K. Sandhoff, K. Harzer, . Wässle, and H. Jatzkewitz, Enzyme Alterations and Lipid Storage in Three Variants of Tay-Sachs Disease, J. Neurochem, vol.18, pp.2469-2489, 1971.

R. A. Gravel, . Kaback, . Mm, . Proia, . Rl et al., The GM2 gangliosidoses. Metab. Mol. Bases Inherit. Dis. III, pp.3827-3876, 2001.

E. F. Neufeld, Natural history and inherited disorders of a lysosomal enzyme, betahexosaminidase, J. Biol. Chem, vol.264, pp.10927-10930, 1989.

K. Sango, S. Yamanaka, A. Hoffmann, Y. Okuda, A. Grinberg et al., Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism, Nat. Genet, vol.11, pp.170-176, 1995.

D. Phaneuf, N. Wakamatsu, J. Huang, A. Borowski, A. C. Peterson et al., Dramatically Different Phenotypes in Mouse Models of Human Tay-Sachs and Sandhoff Diseases, Hum. Mol. Genet, vol.5, pp.1-14, 1996.

J. Huang, J. M. Trasler, S. Igdoura, J. Michaud, . Hanai et al., , 1997.

, Apoptotic Cell Death in Mouse Models of GM2 Gangliosidosis and Observations on Human Tay-Sachs and Sandhoff Diseases, Hum. Mol. Genet, vol.6, pp.1879-1885

R. Wada, . Tifft, and R. L. Proia, Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation, Proc. Natl. Acad. Sci. U. S. A, vol.97, pp.10954-10959, 2000.

M. Jeyakumar, R. Thomas, E. Elliot-smith, . Smith, . Da et al., Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis, Brain, vol.126, pp.974-987, 2003.

K. Matsuoka, T. Tamura, D. Tsuji, Y. Dohzono, K. Kitakaze et al., Therapeutic Potential of Intracerebroventricular Replacement of Modified Human ?-Hexosaminidase B for GM2 Gangliosidosis, Mol. Ther, vol.19, pp.1017-1024, 2011.

G. Maegawa, M. Tropak, J. Butner, T. Stockley, F. Kok et al., Pyrimethamine as a potential pharmacological chaperone for late-onset forms of gm2 gangliosidosis, J. Biol. Chem, vol.282, pp.9150-9161, 2007.

M. Jeyakumar, . Smith, . Da, . Williams, . Im et al., NSAIDs increase survival in the Sandhoff disease mouse: Synergy with Nbutyldeoxynojirimycin, Ann. Neurol, vol.56, pp.642-649, 2004.

. Cachón-gonzález, . Mb, . Wang, . Sz, A. Lynch et al., Effective gene therapy in an authentic model of Tay-Sachs-related diseases, Proc. Natl. Acad. Sci, vol.103, pp.10373-10378, 2006.

. Cachón-gonzález, . Mb, . Wang, . Sz, R. Mcnair et al., Gene Transfer Corrects Acute GM2 Gangliosidosis-Potential Therapeutic Contribution of Perivascular Enzyme Flow, Mol. Ther, vol.20, pp.1489-1500, 2012.

S. Duque, B. Joussemet, C. Riviere, T. Marais, L. Dubreil et al., Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons, Mol. Ther. J. Am. Soc. Gene Ther, vol.17, pp.1187-1196, 2009.

K. D. Foust, E. Nurre, . Montgomery, . Cl, A. Hernandez et al., , 2009.

, Intravascular AAV9 preferentially targets neonatal-neurons and adult-astrocytes in CNS, Nat. Biotechnol, vol.27, pp.59-65

C. F. Valori, K. Ning, M. Wyles, . Mead, . Rj et al., Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy, Sci. Transl. Med, vol.2, pp.35-42, 2010.

K. D. Foust, X. Wang, . Mcgovern, . Vl, L. Braun et al., Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN, Nat. Biotechnol, vol.28, pp.271-274, 2010.

E. Dominguez, T. Marais, N. Chatauret, S. Benkhelifa-ziyyat, S. Duque et al., Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice, Hum. Mol. Genet, vol.20, pp.681-693, 2011.

H. Fu, J. Dirosario, S. Killedar, . Zaraspe, and D. M. Mccarty, Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-bloodbrain barrier gene delivery, Mol. Ther. J. Am. Soc. Gene Ther, vol.19, pp.1025-1033, 2011.

V. Haurigot, S. Marcó, A. Ribera, M. Garcia, A. Ruzo et al., Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy, J. Clin. Invest, 2013.

A. Ruzo, S. Marcó, M. García, P. Villacampa, A. Ribera et al., Correction of Pathological Accumulation of Glycosaminoglycans in Central Nervous System and Peripheral Tissues of MPSIIIA Mice Through Systemic AAV9 Gene Transfer, Hum. Gene Ther, vol.23, pp.1237-1246, 2012.

C. M. Weismann, J. Ferreira, A. M. Keeler, Q. Su, L. Qui et al., , 2015.

, Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan, Hum. Mol. Genet, vol.24, pp.4353-4364

K. Inagaki, S. Fuess, . Storm, . Ta, . Gibson et al., Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8, Mol. Ther. J. Am. Soc. Gene Ther, vol.14, pp.45-53, 2006.

J. S. Walia, N. Altaleb, A. Bello, C. Kruck, . Lafave et al., , 2015.

, Long-Term Correction of Sandhoff Disease Following Intravenous Delivery of rAAV9 to Mouse Neonates, Mol. Ther, vol.23, p.414

N. Armbruster, A. Lattanzi, M. Jeavons, L. Van-wittenberghe, B. Gjata et al., Efficacy and biodistribution analysis of intracerebroventricular administration of an optimized scAAV9-SMN1 vector in a mouse model of spinal muscular atrophy, Mol. Ther. Methods Clin. Dev, vol.3, p.16060, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01487810

A. E. Bley, O. A. Giannikopoulos, D. Hayden, K. Kubilus, C. J. Tifft et al., Natural History of Infantile GM2 Gangliosidosis, vol.128, pp.1233-1241, 2011.

M. B. Cachón-gonzález, S. Z. Wang, R. Mcnair, J. Bradley, D. Lunn et al., Gene Transfer Corrects Acute GM2 Gangliosidosis-Potential Therapeutic Contribution of Perivascular Enzyme Flow, Mol. Ther, vol.20, pp.1489-1500, 2012.

M. Cachón-gonzález, S. Z. Wang, R. Ziegler, S. H. Cheng, and T. M. Cox, , 2014.

, Reversibility of neuropathology in Tay-Sachs-related diseases, Hum. Mol. Genet, vol.23, pp.730-748

R. G. Crystal, D. Sondhi, N. R. Hackett, S. M. Kaminsky, S. Worgall et al., Clinical protocol. Administration of a replication-deficient adeno-associated virus gene transfer vector expressing the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis, Hum. Gene Ther, vol.15, pp.1131-1154, 2004.

S. Duque, B. Joussemet, C. Riviere, T. Marais, L. Dubreil et al., Intravenous administration of selfcomplementary AAV9 enables transgene delivery to adult motor neurons, Mol. Ther. J. Am. Soc. Gene Ther, vol.17, pp.1187-1196, 2009.

J. Fan, A contradictory treatment for lysosomal storage disorders: inhibitors enhance mutant enzyme activity, Trends Pharmacol. Sci, vol.24, pp.355-360, 2003.

K. D. Foust, E. Nurre, C. L. Montgomery, A. Hernandez, C. M. Chan et al., Intravascular AAV9 preferentially targets neonatal-neurons and adult-astrocytes in CNS, Nat. Biotechnol, vol.27, pp.59-65, 2009.

N. Fujita, K. Suzuki, M. T. Vanier, B. Popko, N. Maeda et al., Targeted Disruption of the Mouse Sphingolipid Activator Protein Gene: A Complex Phenotype, Including Severe Leukodystrophy and WideSpread Storage of Multiple Sphingolipids, Hum. Mol. Genet, vol.5, pp.711-725, 1996.

V. Haurigot, S. Marcó, A. Ribera, M. Garcia, A. Ruzo et al., Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy, J. Clin. Invest, vol.123, pp.3254-3271, 2013.

M. Jeyakumar, F. Norflus, C. J. Tifft, M. Cortina-borja, T. D. Butters et al., Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation, Blood, vol.97, pp.327-329, 2001.

M. Jeyakumar, R. Thomas, E. Elliot-smith, D. A. Smith, V. D. Spoel et al., Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis, Brain, vol.126, pp.974-987, 2003.

T. Kyrklund, Two procedures to remove polar contaminants from a crude brain lipid extract by using prepacked reversed-phase columns, Lipids, vol.22, pp.274-277, 1987.

K. Matsuoka, T. Tamura, D. Tsuji, Y. Dohzono, K. Kitakaze et al., Therapeutic potential of intracerebroventricular replacement of modified human ?-hexosaminidase B for GM2 gangliosidosis, Mol. Ther. J. Am. Soc. Gene Ther, vol.19, pp.1017-1024, 2011.

K. Meyer, L. Ferraiuolo, L. Schmelzer, L. Braun, V. Mcgovern et al., Improving Single Injection CSF Delivery of AAV9-mediated Gene Therapy for SMA: A Dose-response Study in Mice and Nonhuman Primates, Mol. Ther, vol.23, pp.477-487, 2015.

F. Mingozzi and K. A. High, Immune responses to AAV vectors: overcoming barriers to successful gene therapy, Blood, vol.122, pp.23-36, 2013.

R. Myerowitz, D. Lawson, H. Mizukami, Y. Mi, C. J. Tifft et al., , 2002.

, Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling, Hum. Mol. Genet, vol.11, pp.1343-1351

F. Norflus, C. J. Tifft, M. P. Mcdonald, G. Goldstein, J. N. Crawley et al., Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice, J. Clin. Invest, vol.101, pp.1881-1888, 1998.

K. J. Osmon, E. Woodley, P. Thompson, K. Ong, S. Karumuthil-melethil et al., Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice, Hum. Gene Ther, vol.27, pp.497-508, 2016.

P. C. Reid, S. Lin, M. T. Vanier, Y. Ohno-iwashita, H. J. Harwood et al., Partial blockage of sterol biosynthesis with a squalene synthase inhibitor in early postnatal Niemann-Pick type C npcnih null mice brains reduces neuronal cholesterol accumulation, abrogates astrogliosis, but may inhibit myelin maturation, J. Neurosci. Methods, vol.168, pp.15-25, 2008.

K. Sandhoff and K. Harzer, Gangliosides and Gangliosidoses: Principles of Molecular and Metabolic Pathogenesis, J. Neurosci, vol.33, pp.10195-10208, 2013.

K. Sandhoff, K. Harzer, W. Wässle, J. , and H. , Enzyme Alterations and Lipid Storage in Three Variants of Tay-Sachs Disease, J. Neurochem, vol.18, pp.2469-2489, 1971.

K. Sango, S. Yamanaka, K. Ajiki, A. Tokashiki, and K. Watabe, Lysosomal storage results in impaired survival but normal neurite outgrowth in dorsal root ganglion neurones from a mouse model of Sandhoff disease, Neuropathol. Appl. Neurobiol, vol.28, pp.23-34, 2002.

C. Spampanato, E. De-leonibus, P. Dama, A. Gargiulo, A. Fraldi et al., Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder, Mol. Ther, vol.19, pp.860-869, 2011.

R. Wada, C. J. Tifft, and R. L. Proia, Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation, Proc. Natl. Acad. Sci. U. S. A, vol.97, pp.10954-10959, 2000.

J. S. Walia, N. Altaleb, A. Bello, C. Kruck, M. C. Lafave et al., Long-Term Correction of Sandhoff Disease Following Intravenous Delivery of rAAV9 to Mouse Neonates, Mol. Ther, vol.23, p.414, 2015.

N. J. Abbott, Blood-brain barrier structure and function and the challenges for CNS drug delivery, J. Inherit. Metab. Dis, vol.36, pp.437-449, 2013.

N. J. Abbott, L. Rönnbäck, and E. Hansson, Astrocyte-endothelial interactions at the blood-brain barrier, Nat. Rev. Neurosci, vol.7, pp.41-53, 2006.

N. J. Abbott, A. A. Patabendige, D. E. Dolman, S. R. Yusof, and D. J. Begley, Structure and function of the blood-brain barrier, Neurobiol. Dis, vol.37, pp.13-25, 2010.

H. Abo-ouf, A. W. Hooper, E. J. White, H. J. Rensburg, . Van et al., Deletion of tumor necrosis factor-? ameliorates neurodegeneration in Sandhoff disease mice, Hum. Mol. Genet, vol.22, pp.3960-3975, 2013.

I. Ahmad, S. Lope-piedrafita, X. Bi, C. Hicks, Y. Yao et al., Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann-Pick C mice, J. Neurosci. Res, vol.82, pp.811-821, 2005.

Z. Akgoc, M. Sena-esteves, D. R. Martin, X. Han, A. Azzo et al., , 2015.

, Bis(monoacylglycero)phosphate: A secondary storage lipid in the gangliosidoses, J. Lipid Res. jlr.M057851

U. Andersson, D. Smith, M. Jeyakumar, T. D. Butters, M. C. Borja et al., Improved outcome of N-butyldeoxygalactonojirimycin-mediated substrate reduction therapy in a mouse model of Sandhoff disease, Neurobiol. Dis, vol.16, pp.506-515, 2004.

S. Ando, Y. Tanaka, S. Kobayashi, F. Fukui, M. Iwamoto et al., Synaptic function of cholinergic-specific Chol-1alpha ganglioside, Neurochem. Res, vol.29, pp.857-867, 2004.

A. Aqul, B. Liu, C. M. Ramirez, A. A. Pieper, S. J. Estill et al., Unesterified Cholesterol Accumulation in Late Endosomes/Lysosomes Causes Neurodegeneration and is Prevented by Driving Cholesterol Export from this Compartment, J. Neurosci. Off. J. Soc. Neurosci, vol.31, pp.9404-9413, 2011.

J. R. Arthur, J. P. Lee, E. Y. Snyder, and T. N. Seyfried, Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff mice, Neurochem. Res, vol.37, pp.1335-1343, 2012.

M. Aschner, Astrocytes as mediators of immune and inflammatory responses in the CNS, Neurotoxicology, vol.19, pp.269-281, 1998.

K. M. Ashe, D. Bangari, L. Li, M. A. Cabrera-salazar, S. D. Bercury et al., Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease, PLoS ONE, vol.6, 2011.

L. Astudillo, F. Sabourdy, N. Therville, H. Bode, B. Ségui et al., Human genetic disorders of sphingolipid biosynthesis, J. Inherit. Metab. Dis, vol.38, pp.65-76, 2015.

R. W. Atchison, B. C. Casto, and W. M. Hammon, Adenovirus-Associated Defective Virus Particles, Science, vol.149, pp.754-755, 1965.
DOI : 10.1126/science.149.3685.754

O. Awad, C. Sarkar, L. M. Panicker, D. Miller, X. Zeng et al., Altered TFEB-mediated lysosomal biogenesis in Gaucher disease iPSC-derived neuronal cells, Hum. Mol. Genet. ddv297, 2015.
DOI : 10.1093/hmg/ddv297
URL : https://academic.oup.com/hmg/article-pdf/24/20/5775/13926858/ddv297.pdf

R. C. Baek, J. L. Kasperzyk, F. M. Platt, and T. N. Seyfried, Nbutyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice, Neurochem. Int, vol.52, pp.1125-1133, 2008.
DOI : 10.1016/j.neuint.2007.12.001

R. C. Baek, D. R. Martin, N. R. Cox, and T. N. Seyfried, Comparative Analysis of Brain Lipids in Mice, Cats, and Humans with Sandhoff Disease, Lipids, vol.44, pp.197-205, 2009.

B. Balakrishnan, R. Jayandharan, and G. , Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy, Curr. Gene Ther, vol.14, pp.86-100, 2014.

A. Ballabio and V. Gieselmann, Lysosomal disorders: From storage to cellular damage, Biochim. Biophys. Acta BBA -Mol. Cell Res, vol.1793, pp.684-696, 2009.

M. Bartel, D. Schaffer, and H. Büning, Enhancing the Clinical Potential of AAV Vectors by Capsid Engineering to Evade Pre-Existing Immunity, Front. Microbiol, vol.2, p.204, 2011.

N. W. Barton, R. O. Brady, J. M. Dambrosia, A. M. Di-bisceglie, S. H. Doppelt et al., Replacement Therapy for Inherited Enzyme Deficiency -Macrophage-Targeted Glucocerebrosidase for Gaucher's Disease, N. Engl. J. Med, vol.324, pp.1464-1470, 1991.

S. Benkhelifa-ziyyat, A. Besse, M. Roda, S. Duque, S. Astord et al., Intramuscular scAAV9-SMN Injection Mediates Widespread Gene Delivery to the Spinal Cord and Decreases Disease Severity in SMA Mice, Mol. Ther, vol.21, pp.282-290, 2013.

I. Ben-sahra and B. D. Manning, mTORC1 signaling and the metabolic control of cell growth, Curr. Opin. Cell Biol, vol.45, pp.72-82, 2017.

K. I. Berns and N. Muzyczka, AAV: An Overview of Unanswered Questions, Hum. Gene Ther, vol.28, pp.308-313, 2017.

J. Berthet and C. De-duve, Tissue fractionation studies. I. The existence of a mitochondria-linked, enzymically inactive form of acid phosphatase in rat-liver tissue, Biochem. J, vol.50, pp.174-181, 1951.

H. L. Best, N. J. Neverman, H. E. Wicky, N. L. Mitchell, B. Leitch et al., Characterisation of early changes in ovine CLN5 and CLN6 Batten disease neural cultures for the rapid screening of therapeutics, Neurobiol. Dis, vol.100, pp.62-74, 2017.

A. E. Bley, O. A. Giannikopoulos, D. Hayden, K. Kubilus, C. J. Tifft et al., Natural History of Infantile GM2 Gangliosidosis, vol.128, pp.1233-1241, 2011.

M. E. Bosch and T. Kielian, Neuroinflammatory paradigms in lysosomal storage diseases, Front. Neurosci, vol.9, 2015.

A. M. Bradbury, J. N. Cochran, V. J. Mccurdy, A. K. Johnson, B. L. Brunson et al., Therapeutic Response in Feline Sandhoff Disease Despite Immunity to Intracranial Gene Therapy, Mol. Ther, vol.21, pp.1306-1315, 2013.

A. M. Bradbury, T. A. Peterson, A. L. Gross, S. Z. Wells, V. J. Mccurdy et al., AAV-mediated gene delivery attenuates neuroinflammation in feline Sandhoff disease, Neuroscience, vol.340, pp.117-125, 2017.

T. Braulke and J. S. Bonifacino, Sorting of lysosomal proteins, Biochim. Biophys. Acta BBA -Mol. Cell Res, vol.1793, pp.605-614, 2009.

D. A. Brown and E. London, Structure and function of sphingolipid-and cholesterolrich membrane rafts, J. Biol. Chem, vol.275, pp.17221-17224, 2000.

N. Brunetti-pierri and P. Ng, Gene therapy with helper-dependent adenoviral vectors: lessons from studies in large animal models, Virus Genes, pp.1-8, 2017.

M. B. Cachón-gonzález, S. Z. Wang, A. Lynch, R. Ziegler, S. H. Cheng et al., Effective gene therapy in an authentic model of Tay-Sachs-related diseases, Proc. Natl. Acad. Sci, vol.103, pp.10373-10378, 2006.

M. Cachón-gonzález, S. Z. Wang, R. Ziegler, S. H. Cheng, and T. M. Cox, , 2014.

, Reversibility of neuropathology in Tay-Sachs-related diseases, Hum. Mol. Genet, vol.23, pp.730-748

R. Calcedo, L. H. Vandenberghe, G. Gao, J. Lin, and J. M. Wilson, Worldwide Epidemiology of Neutralizing Antibodies to Adeno-Associated Viruses, J. Infect. Dis, vol.199, pp.381-390, 2009.

A. Cantore, N. Nair, P. D. Valle, M. D. Matteo, J. Màtrai et al., Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice, Blood, vol.120, pp.4517-4520, 2012.

Y. Cao, J. A. Espinola, E. Fossale, A. C. Massey, A. M. Cuervo et al., Autophagy Is Disrupted in a Knock-in Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis, J. Biol. Chem, vol.281, pp.20483-20493, 2006.

M. J. Castle, H. T. Turunen, L. H. Vandenberghe, and J. H. Wolfe, Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids, Methods Mol. Biol. Clifton NJ, vol.1382, pp.133-149, 2016.

S. Chira, C. S. Jackson, I. Oprea, F. Ozturk, M. S. Pepper et al., Progresses towards safe and efficient gene therapy vectors, Oncotarget, vol.6, pp.30675-30703, 2015.
DOI : 10.18632/oncotarget.5169
URL : http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=5169&path%5B%5D=13374

E. Chiricozzi, N. Niemir, M. Aureli, A. Magini, N. Loberto et al., Chaperone Therapy for GM2 Gangliosidosis: Effects of Pyrimethamine on ?-Hexosaminidase Activity in Sandhoff Fibroblasts, Mol. Neurobiol, vol.50, pp.159-167, 2014.

Y. Chu, H. Dodiya, P. Aebischer, C. W. Olanow, and J. H. Kordower, Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions, Neurobiol. Dis, vol.35, pp.385-398, 2009.
DOI : 10.1016/j.nbd.2009.05.023

J. T. Clarke, D. J. Mahuran, S. Sathe, E. H. Kolodny, B. A. Rigat et al., An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants), Mol. Genet. Metab, vol.102, pp.6-12, 2011.

R. F. Collaco, X. Cao, and J. P. Trempe, A helper virus-free packaging system for recombinant adeno-associated virus vectors, Gene, vol.238, pp.397-405, 1999.
DOI : 10.1016/s0378-1119(99)00347-9

E. Conzelmann, H. J. Kytzia, R. Navon, and K. Sandhoff, Ganglioside GM2 Nacetyl-beta-D-galactosaminidase activity in cultured fibroblasts of late-infantile and adult GM2 gangliosidosis patients and of healthy probands with low hexosaminidase level, Am. J. Hum. Genet, vol.35, pp.900-913, 1983.

M. F. Coutinho, M. J. Prata, and S. Alves, Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction, Mol. Genet. Metab, vol.105, pp.542-550, 2012.

M. F. Coutinho, M. J. Prata, and S. Alves, A shortcut to the lysosome: The mannose-6-phosphate-independent pathway, Mol. Genet. Metab, vol.107, pp.257-266, 2012.

C. Curcio-morelli, F. A. Charles, M. C. Micsenyi, Y. Cao, B. Venugopal et al., Macroautophagy is defective in mucolipin-1-deficient mouse neurons, Neurobiol. Dis, vol.40, pp.370-377, 2010.
DOI : 10.1016/j.nbd.2010.06.010
URL : http://europepmc.org/articles/pmc4392647?pdf=render

D. Dalkara, L. C. Byrne, R. R. Klimczak, M. Visel, L. Yin et al., In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous, Sci. Transl. Med, vol.5, pp.189-76, 2013.

C. D. Davidson, N. F. Ali, M. C. Micsenyi, G. Stephney, S. Renault et al., Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression, PLoS ONE, vol.4, p.6951, 2009.

C. A. Denny, K. A. Heinecke, Y. P. Kim, R. C. Baek, K. S. Loh et al., Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice, J. Neurochem, vol.113, pp.1525-1535, 2010.

D. Deplanque, P. Gelé, O. Pétrault, I. Six, C. Furman et al., Peroxisome Proliferator-Activated Receptor-? Activation as a Mechanism of Preventive Neuroprotection Induced by Chronic Fenofibrate Treatment, J. Neurosci, vol.23, pp.6264-6271, 2003.
URL : https://hal.archives-ouvertes.fr/hal-00537698

R. J. Desnick and E. H. Schuchman, Enzyme replacement and enhancement therapies: lessons from lysosomal disorders, Nat. Rev. Genet, vol.3, pp.954-966, 2002.

R. J. Desnick and E. H. Schuchman, Enzyme Replacement Therapy for Lysosomal Diseases: Lessons from 20 Years of Experience and Remaining Challenges, Annu. Rev. Genomics Hum. Genet, vol.13, pp.307-335, 2012.

B. E. Deverman, P. L. Pravdo, B. P. Simpson, S. R. Kumar, K. Y. Chan et al., Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain, Nat. Biotechnol, vol.34, pp.204-209, 2016.

M. A. Dimattia, H. Nam, K. Van-vliet, M. Mitchell, A. Bennett et al., Structural Insight into the Unique Properties of Adeno-Associated Virus Serotype 9, J. Virol, vol.86, pp.6947-6958, 2012.

A. Donsante, C. Vogler, N. Muzyczka, J. M. Crawford, J. Barker et al., Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors, Gene Ther, vol.8, pp.1343-1346, 2001.

A. Donsante, D. G. Miller, Y. Li, C. Vogler, E. M. Brunt et al., AAV Vector Integration Sites in Mouse Hepatocellular Carcinoma, Science, vol.317, pp.477-477, 2007.

T. Drabek, A. Janata, C. D. Wilson, J. Stezoski, K. Janesko-feldman et al., Minocycline attenuates brain tissue levels of TNF-? produced by neurons after prolonged hypothermic cardiac arrest in rats, Resuscitation, vol.85, pp.284-291, 2014.

N. Dronadula, B. K. Wacker, R. Van-der-kwast, J. Zhang, and D. A. Dichek, Stable In Vivo Transgene Expression in Endothelial Cells with Helper-Dependent Adenovirus: Roles of Promoter and Interleukin-10. Hum, Gene Ther, vol.28, pp.255-270, 2016.

J. El-khoury, M. Toft, S. E. Hickman, T. K. Means, K. Terada et al., Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease, Nat. Med, vol.13, pp.432-438, 2007.

M. Elsabahy, A. Nazarali, and M. Foldvari, Non-viral nucleic acid delivery: key challenges and future directions, Curr. Drug Deliv, vol.8, pp.235-244, 2011.

H. C. Ertl and K. A. High, Impact of AAV Capsid-Specific T-Cell Responses on Design and Outcome of Clinical Gene Transfer Trials with Recombinant Adeno-Associated Viral Vectors: An Evolving Controversy, Hum. Gene Ther, vol.28, pp.328-337, 2016.

S. C. Fagan, D. J. Edwards, C. V. Borlongan, L. Xu, A. Arora et al., Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection, Exp. Neurol, vol.186, pp.248-251, 2004.

J. Fan, S. Ishii, N. Asano, and Y. Suzuki, Accelerated transport and maturation of lysosomal ?-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor, Nat. Med, vol.5, pp.112-115, 1999.

J. D. Finn, T. C. Nichols, N. Svoronos, E. P. Merricks, D. A. Bellenger et al., The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy, Blood, vol.120, pp.4521-4523, 2012.

K. D. Foust, X. Wang, V. L. Mcgovern, L. Braun, A. K. Bevan et al., Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN, Nat. Biotechnol, vol.28, pp.271-274, 2010.

K. D. Foust, D. L. Salazar, S. Likhite, L. Ferraiuolo, D. Ditsworth et al., Therapeutic AAV9-mediated suppression of mutant SOD1 slows disease progression and extends survival in models of inherited ALS, Mol. Ther. J. Am. Soc. Gene Ther, vol.21, pp.2148-2159, 2013.

M. F. Fox, D. L. Dutoit, L. Warnich, and A. E. Retief, Regional localization of alphagalactosidase (GLA) to Xpter----q22, hexosaminidase B (HEXB) to 5q13----qter, and arylsulfatase B (ARSB) to, Cytogenet. Cell Genet, vol.38, pp.45-49, 1984.

A. Fraldi, A. D. Klein, D. L. Medina, and C. Settembre, Brain Disorders Due to Lysosomal Dysfunction, Annu. Rev. Neurosci, vol.39, pp.277-295, 2016.

H. Fu, J. Dirosario, S. Killedar, K. Zaraspe, and D. M. Mccarty, Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-bloodbrain barrier gene delivery, Mol. Ther. J. Am. Soc. Gene Ther, vol.19, pp.1025-1033, 2011.

A. H. Futerman and G. Van-meer, The cell biology of lysosomal storage disorders, Nat. Rev. Mol. Cell Biol, vol.5, pp.554-565, 2004.

H. D. Gallala, B. Breiden, and K. Sandhoff, Regulation of the NPC2 proteinmediated cholesterol trafficking by membrane lipids, J. Neurochem, vol.116, pp.702-707, 2011.

I. G. Ganley, D. H. Lam, J. Wang, X. Ding, S. Chen et al., , 2009.

, ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy, J. Biol. Chem, vol.284, p.12297

G. Gao, L. H. Vandenberghe, M. R. Alvira, Y. Lu, R. Calcedo et al., Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues, J. Virol, vol.78, pp.6381-6388, 2004.

J. V. Gerasimenko, O. V. Gerasimenko, and O. H. Petersen, Membrane repair: Ca(2+)-elicited lysosomal exocytosis, Curr. Biol. CB, vol.11, pp.971-974, 2001.

P. Ghosh, N. M. Dahms, and S. Kornfeld, Mannose 6-phosphate receptors: new twists in the tale, Nat. Rev. Mol. Cell Biol, vol.4, pp.202-213, 2003.

L. Ginzburg, Y. Kacher, and A. H. Futerman, The pathogenesis of glycosphingolipid storage disorders, Semin. Cell Dev. Biol, vol.15, pp.417-431, 2004.

J. J. Glascock, E. Y. Osman, M. J. Wetz, M. M. Krogman, M. Shababi et al., Decreasing disease severity in symptomatic, 2012.

, spinal muscular atrophy mice following scAAV9-SMN delivery, Hum. Gene Ther, vol.23, pp.330-335

D. Golebiowski, I. M. Van-der-bom, C. Kwon, A. D. Miller, K. Petrosky et al., Direct Intracranial Injection of AAVrh8 Encoding Monkey ?-N-Acetylhexosaminidase Causes Neurotoxicity in the Primate Brain, Hum. Gene Ther, vol.28, pp.510-522, 2017.

S. J. Gray, V. Matagne, L. Bachaboina, S. Yadav, S. R. Ojeda et al., , 2011.

, Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates, Mol. Ther. J. Am. Soc. Gene Ther, vol.19, pp.1058-1069

B. Griffin, The use of fecal markers to facilitate sample collection in group-housed cats, Contemp. Top. Lab. Anim. Sci, vol.41, pp.51-56, 2002.

L. D. Griffin, W. Gong, L. Verot, and S. H. Mellon, Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone, Nat. Med, vol.10, pp.704-711, 2004.

J. E. Guidotti, A. Mignon, G. Haase, C. Caillaud, N. Mcdonell et al.,

, Adenoviral Gene Therapy of the Tay-Sachs Disease in Hexosaminidase A-Deficient Knock-Out Mice, Hum. Mol. Genet, vol.8, pp.831-838

D. Guo, J. D. Dunbar, C. H. Yang, L. M. Pfeffer, and D. B. Donner, Induction of Jak/STAT Signaling by Activation of the Type 1 TNF Receptor, J. Immunol, vol.160, pp.2742-2750, 1998.

K. Hanada, K. Kumagai, S. Yasuda, Y. Miura, M. Kawano et al., Molecular machinery for non-vesicular trafficking of ceramide, Nature, vol.426, pp.803-809, 2003.

C. E. Harbison, W. S. Weichert, B. L. Gurda, J. A. Chiorini, M. Agbandje-mckenna et al., Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5, J. Gen. Virol, vol.93, pp.347-355, 2012.

G. V. Harlalka, A. Lehman, B. Chioza, E. L. Baple, R. Maroofian et al., Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis, Brain J. Neurol, vol.136, pp.3618-3624, 2013.

B. Hauck, L. Chen, X. , and W. , Generation and Characterization of Chimeric Recombinant AAV Vectors, Mol. Ther. J. Am. Soc. Gene Ther, vol.7, pp.419-425, 2003.

C. He and D. J. Klionsky, Regulation Mechanisms and Signaling Pathways of Autophagy, Annu. Rev. Genet, vol.43, p.67, 2009.

M. T. Heneka, M. J. Carson, J. E. Khoury, G. E. Landreth, F. Brosseron et al., Neuroinflammation in Alzheimer's disease, vol.14, pp.388-405, 2015.

M. Henkart, Identification and function of intracellular calcium stores in neurons, Fed. Proc, vol.39, pp.2776-2777, 1980.

K. A. Hewlett and D. Corbett, Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia, Neuroscience, vol.141, pp.27-33, 2006.

C. Hinderer, P. Bell, B. L. Gurda, Q. Wang, J. Louboutin et al., Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I, Mol. Ther, vol.22, pp.2018-2027, 2014.

A. W. Hooper and S. A. Igdoura, Bi-phasic gliosis drives neuropathology in a Sandhoff disease mouse model, J. Neuroimmunol, vol.299, pp.19-27, 2016.

A. W. Hooper, J. F. González, R. E. Venier, D. C. Gillespie, and S. A. Igdoura, Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice, Hum. Mol. Genet, vol.26, pp.661-673, 2016.

M. A. Hossain, Hypoxic-Ischemic Injury in Neonatal Brain: Involvement of a Novel Neuronal Molecule in Neuronal Cell Death and Potential Target for Neuroprotection, Int. J. Dev. Neurosci. Off. J. Int. Soc. Dev. Neurosci, vol.26, pp.93-101, 2008.

J. Huang, J. M. Trasler, S. Igdoura, J. Michaud, N. Hanai et al., , 1997.

, Apoptotic Cell Death in Mouse Models of GM2 Gangliosidosis and Observations on Human Tay-Sachs and Sandhoff Diseases, Hum. Mol. Genet, vol.6, pp.1879-1885

S. Ichikawa and Y. Hirabayashi, Glucosylceramide synthase and glycosphingolipid synthesis, Trends Cell Biol, vol.8, pp.198-202, 1998.

L. Izikson, R. S. Klein, I. F. Charo, H. L. Weiner, and A. D. Luster, Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2, J. Exp. Med, vol.192, pp.1075-1080, 2000.

M. Jeyakumar, D. A. Smith, I. M. Williams, M. C. Borja, D. C. Neville et al., NSAIDs increase survival in the Sandhoff disease mouse: Synergy with N-butyldeoxynojirimycin, Ann. Neurol, vol.56, pp.642-649, 2004.

M. Jeyakumar, I. Williams, D. Smith, T. M. Cox, and F. M. Platt, Critical role of iron in the pathogenesis of the murine gangliosidoses, Neurobiol. Dis, vol.34, pp.406-416, 2009.

M. Jeyakumar, J. Lee, N. R. Sibson, J. P. Lowe, D. J. Stuckey et al., Neural stem cell transplantation benefits a monogenic neurometabolic disorder during the symptomatic phase of disease, Stem Cells Dayt. Ohio, vol.27, pp.2362-2370, 2009.

L. Jiang, M. D. Bechtel, J. L. Bean, R. Winefield, T. D. Williams et al., Effects of Gangliosides on the Activity of the Plasma Membrane Ca2+-ATPase, vol.1838, pp.1255-1265, 2014.

W. Jin, S. Feng, Z. Feng, S. Lu, T. Qi et al., Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation, 2013.

E. Jo, S. Li, Q. Liang, X. Zhang, H. Wang et al., Chronic activation of PPAR? with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21, PLoS ONE, vol.12, 2017.

Y. Kanae, D. Endoh, O. Yamato, D. Hayashi, S. Matsunaga et al., Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats, Res. Vet. Sci, vol.82, pp.54-60, 2007.

Y. Kanatsu, N. H. Chen, J. Mitoma, T. Nakagawa, Y. Hirabayashi et al., , 2012.

, Gangliosides stimulate bradykinin B2 receptors to promote calmodulin kinase II-mediated neuronal differentiation, J. Biochem. (Tokyo), vol.152, pp.63-72

S. Kanzaki, A. Yamaguchi, K. Yamaguchi, Y. Kojima, K. Suzuki et al., Thymic Alterations in GM2 Gangliosidoses Model Mice, vol.5, 2010.

S. Kaushik and A. M. Cuervo, Chaperone-mediated autophagy: a unique way to enter the lysosome world, Trends Cell Biol, vol.22, pp.407-417, 2012.

N. Kawashima, D. Tsuji, T. Okuda, K. Itoh, and K. Nakayama, Mechanism of abnormal growth in astrocytes derived from a mouse model of GM2 gangliosidosis, J. Neurochem, vol.111, pp.1031-1041, 2009.

S. Keilani, Y. Lun, A. C. Stevens, H. N. Williams, E. R. Sjoberg et al., Lysosomal Dysfunction in a Mouse Model of Sandhoff Disease Leads to Accumulation of Ganglioside-Bound Amyloid-? Peptide, J. Neurosci, vol.32, pp.5223-5236, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00724557

M. Kohyama, A. Yabuki, Y. Kawasaki, H. Kawaguchi, N. Miura et al., GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog, J. Am. Anim. Hosp. Assoc, vol.51, pp.396-400, 2015.

T. Kolter and K. Sandhoff, Sphingolipid metabolism diseases, Biochim. Biophys. Acta BBA -Biomembr, vol.1758, pp.2057-2079, 2006.

J. B. Koprich, T. H. Johnston, M. G. Reyes, X. Sun, and J. M. Brotchie, Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease, Mol. Neurodegener, vol.5, p.43, 2010.

M. A. Kotterman and D. V. Schaffer, Engineering adeno-associated viruses for clinical gene therapy, Nat. Rev. Genet, vol.15, pp.445-451, 2014.

W. Krivit, Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases, Springer Semin. Immunopathol, vol.26, pp.119-132, 2004.

S. Kyrkanides, A. W. Miller, J. H. Miller, R. H. Tallents, S. M. Brouxhon et al., Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB?/? mouse model of neurodegeneration, J. Neuroimmunol, vol.203, pp.50-57, 2008.

R. H. Lachmann and F. M. Platt, Substrate reduction therapy for glycosphingolipid storage disorders, Expert Opin. Investig. Drugs, vol.10, pp.455-466, 2001.

W. C. Lamanna, R. Lawrence, S. Sarrazin, and J. D. Esko, Secondary Storage of Dermatan Sulfate in Sanfilippo Disease, J. Biol. Chem, vol.286, pp.6955-6962, 2011.

C. A. Lawson and D. R. Martin, Animal models of GM2 gangliosidosis: utility and limitations, Appl. Clin. Genet, vol.9, p.111, 2016.
DOI : 10.2147/tacg.s85354
URL : https://www.dovepress.com/getfile.php?fileID=31457

E. Lecommandeur, D. Baker, T. M. Cox, A. W. Nicholls, and J. L. Griffin, , 2017.

, Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease, J. Lipid Res. jlr.M073395

R. Ledeen and G. Wu, New findings on nuclear gangliosides: overview on metabolism and function, J. Neurochem, vol.116, pp.714-720, 2011.
DOI : 10.1111/j.1471-4159.2010.07115.x
URL : https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2010.07115.x

H. Lee, C. Chi, and C. Tsai, Early cardiac involvement in an infantile Sandhoff disease case with novel mutations, Brain Dev, vol.39, pp.171-176, 2017.
DOI : 10.1016/j.braindev.2016.09.006

J. Lee, M. Jeyakumar, R. Gonzalez, H. Takahashi, P. Lee et al., Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease, Nat. Med, vol.13, pp.439-447, 2007.
DOI : 10.1038/nm1548

G. Liao, Y. Yao, J. Liu, Z. Yu, S. Cheung et al., , 2007.

, Cholesterol Accumulation Is Associated with Lysosomal Dysfunction and Autophagic Stress in Npc1?/? Mouse Brain, Am. J. Pathol, vol.171, pp.962-975

G. P. Lim, F. Yang, T. Chu, P. Chen, W. Beech et al., Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease, J. Neurosci. Off. J. Soc. Neurosci, vol.20, pp.5709-5714, 2000.
DOI : 10.1523/jneurosci.20-15-05709.2000
URL : http://www.jneurosci.org/content/jneuro/20/15/5709.full.pdf

G. P. Lim, F. Yang, T. Chu, E. Gahtan, O. Ubeda et al., Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice, Neurobiol. Aging, vol.22, pp.983-991, 2001.
DOI : 10.1016/s0197-4580(01)00299-8

J. Lim, L. Li, O. S. Shirihai, K. M. Trudeau, R. Puertollano et al., , 2017.

, Modulation of mTOR signaling as a strategy for the treatment of Pompe disease, EMBO Mol. Med, vol.9, pp.353-370

M. P. Limberis, L. H. Vandenberghe, L. Zhang, R. J. Pickles, and J. M. Wilson, , 2009.

, Transduction Efficiencies of Novel AAV Vectors in Mouse Airway Epithelium In Vivo and Human Ciliated Airway Epithelium In Vitro, Mol. Ther. J. Am. Soc. Gene Ther, vol.17, pp.294-301

L. Lisowski, S. S. Tay, A. , and I. E. , Adeno-associated virus serotypes for gene therapeutics, Curr. Opin. Pharmacol, vol.24, pp.59-67, 2015.
DOI : 10.1016/j.coph.2015.07.006

B. Liu, C. M. Ramirez, A. M. Miller, J. J. Repa, S. D. Turley et al., , 2010.

, Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid, J. Lipid Res, vol.51, pp.933-944

Y. Liu, R. Wada, H. Kawai, K. Sango, C. Deng et al., A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder, J. Clin. Invest, vol.103, pp.497-505, 1999.

E. Lukina, N. Watman, E. A. Arreguin, M. Banikazemi, M. Dragosky et al., A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1, Blood, vol.116, pp.893-899, 2010.

J. P. Luzio, P. R. Pryor, and N. A. Bright, Lysosomes: fusion and function, Nat. Rev. Mol. Cell Biol, vol.8, pp.622-632, 2007.
DOI : 10.1038/nrm2217

G. H. Maegawa, M. Tropak, J. Butner, T. Stockley, F. Kok et al., Pyrimethamine as a potential pharmacological chaperone for late-onset forms of gm2 gangliosidosis, J. Biol. Chem, vol.282, pp.9150-9161, 2007.
DOI : 10.1074/jbc.m609304200
URL : http://www.jbc.org/content/282/12/9150.full.pdf

D. Maetzel, S. Sarkar, H. Wang, L. Abi-mosleh, P. Xu et al., Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived from Niemann-Pick Type C Patient-Specific iPS Cells, Stem Cell Rep, vol.2, pp.866-880, 2014.

M. Ohsawa, M. Kotani, Y. Tajima, D. Tsuji, Y. Ishibashi et al., Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human ?-hexosaminidase A on the accumulated GM2 ganglioside, J. Hum. Genet, vol.50, pp.460-467, 2005.

F. P. Manfredsson, A. C. Rising, and R. J. Mandel, AAV9: a potential blood-brain barrier buster, Mol. Ther. J. Am. Soc. Gene Ther, vol.17, pp.403-405, 2009.
DOI : 10.1038/mt.2009.15
URL : https://doi.org/10.1038/mt.2009.15

C. S. Manno, F. Glenn, . Pierce, V. R. Arruda, G. F. Pierce et al., Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response, Nat. Med, vol.12, pp.342-347, 2006.

B. L. Mark, D. J. Mahuran, M. M. Cherney, D. Zhao, S. Knapp et al., , 2003.

, Crystal Structure of Human ?-Hexosaminidase B: Understanding the Molecular Basis of Sandhoff and Tay-Sachs Disease, J. Mol. Biol, vol.327, pp.1093-1109

D. R. Martin, B. K. Krum, G. S. Varadarajan, T. L. Hathcock, B. F. Smith et al., An inversion of 25 base pairs causes feline GM2 gangliosidosis variant, Exp. Neurol, vol.187, pp.30-37, 2004.
DOI : 10.1016/j.expneurol.2004.01.008

J. A. Martiney, C. Cuff, M. Litwak, J. Berman, and C. F. Brosnan, Cytokine-induced inflammation in the central nervous system revisited, Neurochem. Res, vol.23, pp.349-359, 1998.

M. Martinez-vicente and A. M. Cuervo, Autophagy and neurodegeneration: when the cleaning crew goes on strike, Lancet Neurol, vol.6, pp.352-361, 2007.
DOI : 10.1016/s1474-4422(07)70076-5

H. Martini-stoica, Y. Xu, A. Ballabio, and H. Zheng, The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective, Trends Neurosci, vol.39, pp.221-234, 2016.

M. Masciullo, M. Santoro, A. Modoni, E. Ricci, J. Guitton et al., Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up, J. Inherit. Metab. Dis, vol.33, pp.355-361, 2010.

K. Matsuoka, D. Tsuji, T. Taki, and K. Itoh, Thymic involution and corticosterone level in Sandhoff disease model mice: new aspects the pathogenesis of GM2 gangliosidosis, J. Inherit. Metab. Dis, vol.34, pp.1061-1068, 2011.

D. M. Mccarty, Self-complementary AAV vectors; advances and applications, Mol. Ther. J. Am. Soc. Gene Ther, vol.16, pp.1648-1656, 2008.

D. M. Mccarty, H. Fu, P. E. Monahan, C. E. Toulson, P. Naik et al., , 2003.

, Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo, Gene Ther, vol.10, pp.2112-2118

V. J. Mccurdy, H. E. Rockwell, J. R. Arthur, A. M. Bradbury, A. K. Johnson et al., Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease, Gene Ther, vol.22, pp.181-189, 2015.

P. L. Mcgeer and E. G. Mcgeer, Local neuroinflammation and the progression of Alzheimer's disease, J. Neurovirol, vol.8, pp.529-538, 2002.

D. L. Medina, A. Fraldi, V. Bouche, F. Annunziata, G. Mansueto et al., Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular Clearance, Dev. Cell, vol.21, pp.421-430, 2011.

P. J. Meikle, J. J. Hopwood, A. E. Clague, and W. F. Carey, Prevalence of lysosomal storage disorders, JAMA, vol.281, pp.249-254, 1999.

Y. Meng, I. Sohar, D. E. Sleat, J. R. Richardson, K. R. Reuhl et al., Effective Intravenous Therapy for Neurodegenerative Disease With a Therapeutic Enzyme and a Peptide That Mediates Delivery to the Brain, Mol. Ther, vol.22, pp.547-553, 2014.

F. M. Menzies, A. Fleming, and D. C. Rubinsztein, Compromised autophagy and neurodegenerative diseases, Nat. Rev. Neurosci, vol.16, pp.345-357, 2015.

D. Mijaljica, M. Prescott, and R. J. Devenish, Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum, Autophagy, vol.7, pp.673-682, 2011.

E. I. Miklyaeva, W. Dong, A. Bureau, R. Fattahie, Y. Xu et al., Late onset Tay-Sachs disease in mice with targeted disruption of the Hexa gene: behavioral changes and pathology of the central nervous system, Brain Res, vol.1001, pp.37-50, 2004.

E. A. Miljan and E. G. Bremer, Regulation of growth factor receptors by gangliosides, Sci. STKE Signal Transduct. Knowl. Environ, p.15, 2002.

F. Mingozzi, N. C. Hasbrouck, E. Basner-tschakarjan, S. A. Edmonson, D. J. Hui et al., Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver, Blood, vol.110, pp.2334-2341, 2007.

F. Mingozzi, M. V. Maus, D. J. Hui, D. E. Sabatino, S. L. Murphy et al., CD8(+) T-cell responses to adenoassociated virus capsid in humans, Nat. Med, vol.13, pp.419-422, 2007.

F. Mingozzi, X. M. Anguela, G. Pavani, Y. Chen, R. J. Davidson et al., Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys, Sci. Transl. Med, vol.5, pp.194-92, 2013.

F. Mingozzi, Y. Chen, S. C. Edmonson, S. Zhou, R. M. Thurlings et al., Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue, Gene Ther, vol.20, pp.417-424, 2013.

C. M. Misquitta, D. P. Mack, and A. K. Grover, Sarco/endoplasmic reticulum Ca2+ (SERCA)-pumps: link to heart beats and calcium waves, Cell Calcium, vol.25, pp.277-290, 1999.

N. Miyake, K. Miyake, N. Asakawa, M. Yamamoto, and T. Shimada, Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector, Gene Ther, vol.21, pp.427-433, 2014.

A. L. Montalvo, M. Filocamo, K. Vlahovicek, A. Dardis, S. Lualdi et al., Molecular analysis of the HEXA gene in Italian patients with infantile and late onset Tay-Sachs disease: detection of fourteen novel alleles, Hum. Mutat, vol.26, p.282, 2005.

M. Moskot, S. Montefusco, J. Jakóbkiewicz-banecka, P. Mozolewski, A. W?grzyn et al., The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation, J. Biol. Chem, vol.289, pp.17054-17069, 2014.

J. D. Mount, R. W. Herzog, D. M. Tillson, S. A. Goodman, N. Robinson et al., Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy, Blood, vol.99, pp.2670-2676, 2002.

S. Munro, Lipid rafts: elusive or illusive?, Cell, vol.115, pp.377-388, 2003.

G. Murlidharan, R. J. Samulski, A. , and A. , Biology of adeno-associated viral vectors in the central nervous system, Front. Mol. Neurosci, vol.7, 2014.

R. Myerowitz and F. C. Costigan, The major defect in Ashkenazi Jews with TaySachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase, J. Biol. Chem, vol.263, pp.18587-18589, 1988.

R. Myerowitz and N. D. Hogikyan, A deletion involving Alu sequences in the betahexosaminidase alpha-chain gene of French Canadians with Tay-Sachs disease, J. Biol. Chem, vol.262, pp.15396-15399, 1987.

R. Myerowitz, D. Lawson, H. Mizukami, Y. Mi, C. J. Tifft et al., , 2002.

, Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling, Hum. Mol. Genet, vol.11, pp.1343-1351

A. C. Nathwani, E. G. Tuddenham, S. Rangarajan, C. Rosales, J. Mcintosh et al., Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Hemophilia B, N. Engl. J. Med, vol.365, pp.2357-2365, 2011.
DOI : 10.1056/nejmoa1108046
URL : https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/27163/1/Pasi%20Adenovirus-associated%20virus%20vector-mediated%202011%20Publisher.pdf

R. Navon and R. L. Proia, The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease, Science, vol.243, pp.1471-1474, 1989.

K. Neote, B. Mcinnes, D. J. Mahuran, and R. A. Gravel, Structure and distribution of an Alu-type deletion mutation in Sandhoff disease, J. Clin. Invest, vol.86, pp.1524-1531, 1990.

E. E. Netland, J. L. Newton, R. E. Majocha, and B. A. Tate, Indomethacin Reverses the Microglial Response to Amyloid ?-Protein, Neurobiol. Aging, vol.19, pp.201-204, 1998.
DOI : 10.1016/s0197-4580(98)00047-5

E. A. Neuwelt, W. G. Johnson, N. K. Blank, M. A. Pagel, C. Maslen-mcclure et al., Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats, J. Clin. Invest, vol.76, pp.482-490, 1985.

R. A. Nixon, Autophagy, amyloidogenesis and Alzheimer disease, J. Cell Sci, vol.120, pp.4081-4091, 2007.
DOI : 10.1242/jcs.019265
URL : http://jcs.biologists.org/content/120/23/4081.full.pdf

R. A. Nixon, D. Yang, and J. Lee, Neurodegenerative lysosomal disorders: a continuum from development to late age, Autophagy, vol.4, pp.590-599, 2008.
DOI : 10.4161/auto.6259

Y. Ohmi, O. Tajima, Y. Ohkawa, A. Mori, Y. Sugiura et al., Gangliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues, Proc. Natl. Acad. Sci. U. S. A, vol.106, pp.22405-22410, 2009.

L. D. Osellame, A. A. Rahim, I. P. Hargreaves, M. E. Gegg, A. Richard-londt et al., Mitochondria and Quality Control Defects in a Mouse Model of Gaucher Disease-Links to Parkinson's Disease, Cell Metab, vol.17, pp.941-953, 2013.

R. De-pablo-latorre, A. Saide, E. V. Polishhuck, E. Nusco, A. Fraldi et al., Impaired parkin-mediated mitochondrial targeting to autophagosomes differentially contributes to tissue pathology in lysosomal storage diseases, Hum. Mol. Genet, vol.21, pp.1770-1781, 2012.

M. Palmieri, S. Impey, H. Kang, A. Di-ronza, C. Pelz et al., Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways, Hum. Mol. Genet, vol.20, pp.3852-3866, 2011.

B. H. Paw, P. T. Tieu, M. M. Kaback, J. Lim, and E. F. Neufeld, Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program, Am. J. Hum. Genet, vol.47, pp.698-705, 1990.

D. Pelled, E. Lloyd-evans, C. Riebeling, M. Jeyakumar, F. M. Platt et al., Inhibition of Calcium Uptake via the Sarco/Endoplasmic Reticulum Ca2+-ATPase in a Mouse Model of Sandhoff Disease and Prevention by Treatment with NButyldeoxynojirimycin, J. Biol. Chem, vol.278, pp.29496-29501, 2003.

R. Penati, F. Fumagalli, V. Calbi, M. E. Bernardo, A. et al., Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I, J. Inherit. Metab. Dis, pp.1-12, 2017.

V. H. Perry, S. J. Bolton, D. C. Anthony, and S. Betmouni, The contribution of inflammation to acute and chronic neurodegeneration, Res. Immunol, vol.149, pp.721-725, 1998.

G. C. Pien, E. Basner-tschakarjan, D. J. Hui, A. N. Mentlik, J. D. Finn et al., Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors, J. Clin. Invest, vol.119, pp.1688-1695, 2009.
DOI : 10.1172/jci36891
URL : http://europepmc.org/articles/pmc2689109?pdf=render

R. Pincheira, A. F. Castro, O. N. Ozes, P. S. Idumalla, and D. B. Donner, Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity, J. Immunol, vol.181, pp.1288-1298, 2008.
DOI : 10.4049/jimmunol.181.2.1288
URL : http://www.jimmunol.org/content/181/2/1288.full.pdf

F. M. Platt, G. R. Neises, G. Reinkensmeier, M. J. Townsend, V. H. Perry et al., Prevention of Lysosomal Storage in Tay-Sachs Mice Treated with N-Butyldeoxynojirimycin, Science, vol.276, pp.428-431, 1997.

F. M. Platt, B. Boland, and A. C. Van-der-spoel, Lysosomal storage disorders: The cellular impact of lysosomal dysfunction, J. Cell Biol, vol.199, pp.723-734, 2012.
DOI : 10.1083/jcb.201208152
URL : http://jcb.rupress.org/content/199/5/723.full.pdf

A. Prinetti, K. Iwabuchi, and S. Hakomori, Glycosphingolipid-enriched signaling domain in mouse neuroblastoma Neuro2a cells. Mechanism of ganglioside-dependent neuritogenesis, J. Biol. Chem, vol.274, pp.20916-20924, 1999.
DOI : 10.1074/jbc.274.30.20916
URL : http://www.jbc.org/content/274/30/20916.full.pdf

A. Prinetti, S. Prioni, E. Chiricozzi, E. H. Schuchman, V. Chigorno et al., Secondary Alterations of Sphingolipid Metabolism in Lysosomal Storage Diseases, Neurochem. Res, vol.36, pp.1654-1668, 2011.

M. M. Rahman, H. Chang, K. Mizukami, M. A. Hossain, A. Yabuki et al., A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease), Vet. J, vol.194, pp.412-416, 2012.

B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-arencibia et al., Regulation of Mammalian Autophagy in Physiology and Pathophysiology, Physiol. Rev, vol.90, pp.1383-1435, 2010.

A. Reddy, E. V. Caler, and N. W. Andrews, Plasma Membrane Repair Is Mediated by Ca2+-Regulated Exocytosis of Lysosomes, Cell, vol.106, pp.157-169, 2001.
DOI : 10.1016/s0092-8674(01)00421-4
URL : https://doi.org/10.1016/s0092-8674(01)00421-4

E. Régulier, B. L. Schneider, N. Déglon, Y. Beuzard, and P. Aebischer, Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts, Gene Ther, vol.5, pp.1014-1022, 1998.

D. Renaud and M. Brodsky, GM2-Gangliosidosis, AB Variant: Clinical, Ophthalmological, MRI, and Molecular Findings, JIMD Rep, vol.25, pp.83-86, 2016.
DOI : 10.1007/8904_2015_469
URL : http://europepmc.org/articles/pmc5059184?pdf=render

A. Ribera, V. Haurigot, M. Garcia, S. Marcó, S. Motas et al., Biochemical, histological and functional correction of mucopolysaccharidosis Type IIIB by intra-cerebrospinal fluid gene therapy, Hum. Mol. Genet, vol.24, pp.2078-2095, 2015.

H. E. Rockwell, V. J. Mccurdy, S. C. Eaton, D. U. Wilson, A. K. Johnson et al., AAVMediated Gene Delivery in a Feline Model of Sandhoff Disease Corrects Lysosomal Storage in the Central Nervous System, ASN Neuro, vol.7, 2015.

D. C. Rubinsztein, P. Codogno, and B. Levine, Autophagy modulation as a potential therapeutic target for diverse diseases, Nat. Rev. Drug Discov, vol.11, pp.709-730, 2012.
DOI : 10.1038/nrd3802
URL : http://europepmc.org/articles/pmc3518431?pdf=render

F. Sabourdy, L. Astudillo, C. Colacios, P. Dubot, M. Mrad et al., Monogenic neurological disorders of sphingolipid metabolism, Biochim. Biophys. Acta BBA -Mol. Cell Biol. Lipids, vol.1851, pp.1040-1051, 2015.
DOI : 10.1016/j.bbalip.2015.01.010

P. Saftig and J. Klumperman, Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function, Nat. Rev. Mol. Cell Biol, vol.10, pp.623-635, 2009.
DOI : 10.1038/nrm2745

K. Sandhoff and K. Harzer, Gangliosides and Gangliosidoses: Principles of Molecular and Metabolic Pathogenesis, J. Neurosci, vol.33, pp.10195-10208, 2013.

M. R. Santos, A. Tanaka, M. C. Sá-miranda, M. G. Ribeiro, M. Maia et al.,

, GM2-gangliosidosis B1 variant: analysis of beta-hexosaminidase alpha gene mutations in 11 patients from a defined region in Portugal, Am. J. Hum. Genet, vol.49, pp.886-890

J. Saraiva, R. J. Nobre, and L. Pereira-de-almeida, Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9, J. Controlled Release, vol.241, pp.94-109, 2016.

M. Sardiello, M. Palmieri, A. Ronza, . Di, D. L. Medina et al., A Gene Network Regulating Lysosomal Biogenesis and Function, Science, vol.325, pp.473-477, 2009.

T. J. Sargeant, S. Wang, J. Bradley, N. J. Smith, A. A. Raha et al., Adeno-associated virusmediated expression of ?-hexosaminidase prevents neuronal loss in the Sandhoff mouse brain, Hum. Mol. Genet, vol.20, pp.4371-4380, 2011.

S. Sarkar, Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers, Biochem. Soc. Trans, vol.41, pp.1103-1130, 2013.

C. Schengrund, Gangliosides: glycosphingolipids essential for normal neural development and function, Trends Biochem. Sci, vol.40, pp.397-406, 2015.

U. Schepers, G. Glombitza, T. Lemm, A. Hoffmann, A. Chabas et al., Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant, Am. J. Hum. Genet, vol.59, pp.1048-1056, 1996.

M. Schröder, D. Schnabel, K. Suzuki, and K. Sandhoff, A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB, FEBS Lett, vol.290, pp.1-3, 1991.

M. Schröder, D. Schnabel, R. Hurwitz, E. Young, K. Suzuki et al., Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells, Hum. Genet, vol.92, pp.437-440, 1993.

C. Settembre, A. Fraldi, L. Jahreiss, C. Spampanato, C. Venturi et al., A block of autophagy in lysosomal storage disorders, Hum. Mol. Genet, vol.17, pp.119-129, 2008.

C. Settembre, C. Di-malta, V. A. Polito, M. Garcia-arencibia, F. Vetrini et al., TFEB links autophagy to lysosomal biogenesis, vol.332, pp.1429-1433, 2011.

C. Settembre, R. Zoncu, D. L. Medina, F. Vetrini, S. Erdin et al., A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB, EMBO J, vol.31, pp.1095-1108, 2012.

C. Settembre, A. Fraldi, D. L. Medina, and A. Ballabio, Signals from the lysosome: a control centre for cellular clearance and energy metabolism, Nat. Rev. Mol. Cell Biol, vol.14, pp.283-296, 2013.

C. Settembre, R. D. Cegli, G. Mansueto, P. K. Saha, F. Vetrini et al., TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop, Nat. Cell Biol, vol.15, p.647, 2013.

V. Seyrantepe, M. Canuel, S. Carpentier, K. Landry, S. Durand et al., Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage, Hum. Mol. Genet, vol.17, pp.1556-1568, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00409398

V. Seyrantepe, P. Lema, A. Caqueret, L. Dridi, S. Bel-hadj et al., Mice Doubly-Deficient in Lysosomal Hexosaminidase A and Neuraminidase 4 Show Epileptic Crises and Rapid Neuronal Loss, PLoS Genet, vol.6, 2010.

M. Simonato, J. Bennett, N. M. Boulis, M. G. Castro, D. J. Fink et al., Progress in gene therapy for neurological disorders, Nat. Rev. Neurol, vol.9, pp.277-291, 2013.

M. A. Simpson, H. Cross, C. Proukakis, D. A. Priestman, D. C. Neville et al., Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase, Nat. Genet, vol.36, pp.1225-1229, 2004.

D. Smith, K. Wallom, I. M. Williams, M. Jeyakumar, and F. M. Platt, Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1, Neurobiol. Dis, vol.36, pp.242-251, 2009.

W. Song, F. Wang, P. Lotfi, M. Sardiello, and L. Segatori, 2-Hydroxypropyl-?-cyclodextrin Promotes Transcription Factor EB-mediated Activation of Autophagy: IMPLICATIONS FOR THERAPY, J. Biol. Chem, vol.289, pp.10211-10222, 2014.

C. Spampanato, E. Feeney, L. Li, M. Cardone, J. Lim et al., Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease, EMBO Mol. Med, vol.5, pp.691-706, 2013.
DOI : 10.1002/emmm.201202176
URL : http://embomolmed.embopress.org/content/5/5/691.full.pdf

A. Stein, S. Stroobants, V. Gieselmann, R. D'hooge, and U. Matzner, Antiinflammatory Therapy With Simvastatin Improves Neuroinflammation and CNS Function in a Mouse Model of Metachromatic Leukodystrophy, Mol. Ther, vol.23, pp.1160-1168, 2015.

D. P. Stirling, Minocycline Treatment Reduces Delayed Oligodendrocyte Death, Attenuates Axonal Dieback, and Improves Functional Outcome after Spinal Cord Injury, J. Neurosci, vol.24, pp.2182-2190, 2004.
DOI : 10.1523/jneurosci.5275-03.2004
URL : http://www.jneurosci.org/content/24/9/2182.full.pdf

K. Suzuki, A. Yamaguchi, S. Yamanaka, S. Kanzaki, M. Kawashima et al., Accumulated ?-synuclein affects the progression of GM2 gangliosidoses, Exp. Neurol, vol.284, pp.38-49, 2016.

A. Takamura, K. Higaki, K. Kajimaki, S. Otsuka, H. Ninomiya et al., Enhanced autophagy and mitochondrial aberrations in murine GM1-gangliosidosis, Biochem. Biophys. Res. Commun, vol.367, pp.616-622, 2008.
DOI : 10.1016/j.bbrc.2007.12.187

H. Takeuchi, S. Jin, J. Wang, G. Zhang, J. Kawanokuchi et al., Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner, J. Biol. Chem, vol.281, pp.21362-21368, 2006.

C. M. Tallaksen and J. E. Berg, Miglustat therapy in juvenile Sandhoff disease, J. Inherit. Metab. Dis, vol.32, pp.289-293, 2009.
DOI : 10.1007/s10545-009-1224-7

Y. Tanguy, M. G. Biferi, A. Besse, S. Astord, M. Cohen-tannoudji et al., Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice, Front. Mol. Neurosci, vol.8, 2015.

M. Thomas, J. , and J. , Neurodegenerative disease and iron storage in the brain, Curr. Opin. Neurol, vol.17, pp.437-442, 2004.

G. M. Thomsen, G. Gowing, J. Latter, M. Chen, J. Vit et al., Delayed disease onset and extended survival in the SOD1G93A rat model of amyotrophic lateral sclerosis after suppression of mutant SOD1 in the motor cortex, J. Neurosci. Off. J. Soc. Neurosci, vol.34, pp.15587-15600, 2014.

P. A. Torres, B. J. Zeng, B. F. Porter, J. Alroy, F. Horak et al., Tay-Sachs disease in Jacob sheep, Mol. Genet. Metab, vol.101, pp.357-363, 2010.
DOI : 10.1016/j.ymgme.2010.08.006

B. Triggs-raine, D. J. Mahuran, and R. A. Gravel, Naturally occurring mutations in GM2 gangliosidosis: a compendium, Adv. Genet, vol.44, pp.199-224, 2001.

M. B. Tropak, S. P. Reid, M. Guiral, S. G. Withers, and D. Mahuran, , 2004.

, Pharmacological Enhancement of ?-Hexosaminidase Activity in Fibroblasts from Adult TaySachs and Sandhoff Patients, J. Biol. Chem, vol.279, pp.13478-13487

M. B. Tropak, J. Zhang, S. Yonekawa, B. A. Rigat, V. S. Aulakh et al., Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant ?-N-acetylhexosaminidase Activity, J. Med. Chem, vol.58, pp.4483-4493, 2015.
DOI : 10.1021/jm5017895

L. V. Tse, S. Moller-tank, A. , and A. , Strategies to circumvent humoral immunity to adeno-associated viral vectors, Expert Opin. Biol. Ther, vol.15, pp.845-855, 2015.
DOI : 10.1517/14712598.2015.1035645
URL : http://europepmc.org/articles/pmc4689135?pdf=render

T. Tsunemi, T. D. Ashe, B. E. Morrison, K. R. Soriano, J. Au et al., PGC-1? rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function, Sci. Transl. Med, vol.4, pp.142-97, 2012.
DOI : 10.1126/scitranslmed.3003799
URL : http://europepmc.org/articles/pmc4096245?pdf=render

J. R. Utz, T. Crutcher, J. Schneider, P. Sorgen, and C. B. Whitley, Biomarkers of Central Nervous System Inflammation in Infantile and Juvenile Gangliosidoses, vol.114, p.274, 2015.

C. F. Valori, K. Ning, M. Wyles, R. J. Mead, A. J. Grierson et al., Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy, Sci. Transl. Med, vol.2, pp.35-42, 2010.

S. Vergarajauregui, P. S. Connelly, M. P. Daniels, and R. Puertollano, Autophagic dysfunction in mucolipidosis type IV patients, Hum. Mol. Genet, vol.17, pp.2723-2737, 2008.

I. T. Villamizar-schiller, L. A. Pabón, S. B. Hufnagel, N. C. Serrano, G. Karl et al., Neurological and cardiac responses after treatment with miglustat and a ketogenic diet in a patient with Sandhoff disease, Eur. J. Med. Genet, vol.58, pp.180-183, 2015.

C. H. Vite, M. A. Passini, M. E. Haskins, and J. H. Wolfe, Adeno-associated virus vector-mediated transduction in the cat brain, Gene Ther, vol.10, pp.1874-1881, 2003.

J. S. Walia, N. Altaleb, A. Bello, C. Kruck, M. C. Lafave et al., Long-Term Correction of Sandhoff Disease Following Intravenous Delivery of rAAV9 to Mouse Neonates, Mol. Ther, vol.23, p.414, 2015.

S. U. Walkley and M. T. Vanier, Pathomechanisms in Lysosomal Storage Disorders, Biochim. Biophys. Acta, vol.1793, pp.726-736, 2009.

Y. Wang and Z. Qin, Molecular and cellular mechanisms of excitotoxic neuronal death, Apoptosis Int. J. Program. Cell Death, vol.15, pp.1382-1402, 2010.

C. M. Weismann, J. Ferreira, A. M. Keeler, Q. Su, L. Qui et al., Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan, Hum. Mol. Genet, vol.24, pp.4353-4364, 2015.

M. Wendeler, J. Hoernschemeyer, D. Hoffmann, T. Kolter, G. Schwarzmann et al., Photoaffinity labelling of the Human GM2-activator protein, Eur. J. Biochem, vol.271, pp.614-627, 2004.

S. B. Wortmann, D. J. Lefeber, G. Dekomien, M. Willemsen, .. P. Wevers et al., Substrate deprivation therapy in juvenile Sandhoff disease, J. Inherit. Metab. Dis, vol.32, pp.307-311, 2009.

Y. Wu and R. L. Proia, Deletion of macrophage-inflammatory protein 1? retards neurodegeneration in Sandhoff disease mice, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.8425-8430, 2004.

Y. Wu, K. Mizugishi, M. Bektas, R. Sandhoff, and R. L. Proia, Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease, Hum. Mol. Genet, vol.17, pp.2257-2264, 2008.

X. Xiao, W. Xiao, J. Li, and R. J. Samulski, A novel 165-base-pair terminal repeat sequence is the sole cis requirement for the adeno-associated virus life cycle, J. Virol, vol.71, pp.941-948, 1997.

A. Yamaguchi, K. Katsuyama, K. Nagahama, T. Takai, I. Aoki et al., , 2004.

, Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses, J. Clin. Invest, vol.113, pp.200-208

S. Yamanaka, M. D. Johnson, A. Grinberg, H. Westphal, J. N. Crawley et al., Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease, Proc. Natl. Acad. Sci. U. S. A, vol.91, pp.9975-9979, 1994.

O. Yamato, N. Matsuki, H. Satoh, M. Inaba, K. Ono et al., Sandhoff disease in a golden retriever dog, J. Inherit. Metab. Dis, vol.25, pp.319-320, 2002.

O. Yamato, D. Hayashi, H. Satoh, T. Shoda, K. Uchida et al., Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan: possible spread of the mutant allele in the Japanese domestic cat population, J. Vet. Med. Sci, vol.70, pp.813-818, 2008.

L. Yu, C. K. Mcphee, L. Zheng, G. A. Mardones, Y. Rong et al., Termination of autophagy and reformation of lysosomes regulated by mTOR, Nature, vol.465, pp.942-946, 2010.

R. K. Yu, Y. Tsai, T. Ariga, Y. , and M. , Structures, biosynthesis, and functions of gangliosides-An overview, J. Oleo Sci, vol.60, p.537, 2011.

J. Zabner, S. C. Wadsworth, A. E. Smith, and M. J. Welsh, Adenovirus-mediated generation of cAMP-stimulated Cl-transport in cystic fibrosis airway epithelia in vitro: effect of promoter and administration method, Gene Ther, vol.3, pp.458-465, 1996.

B. J. Zeng, P. A. Torres, T. C. Viner, Z. H. Wang, S. S. Raghavan et al., Spontaneous appearance of Tay-Sachs disease in an animal model, Mol. Genet. Metab, vol.95, pp.59-65, 2008.

G. Zhang, H. C. Lehmann, S. Manoharan, M. Hashmi, S. Shim et al., Anti-ganglioside antibodymediated activation of RhoA induces inhibition of neurite outgrowth, J. Neurosci. Off. J. Soc. Neurosci, vol.31, pp.1664-1675, 2011.

L. Zhong, B. Li, C. S. Mah, L. Govindasamy, M. Agbandje-mckenna et al., Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to highefficiency transduction at lower doses, Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.7827-7832, 2008.

D. Zhou, J. Mattner, C. Cantu, N. Schrantz, N. Yin et al., Lysosomal Glycosphingolipid Recognition by NKT Cells, Science, vol.306, pp.1786-1789, 2004.

R. Zoncu, L. Bar-peled, A. Efeyan, S. Wang, Y. Sancak et al., mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the Vacuolar H+-ATPase, Science, vol.334, pp.678-683, 2011.