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, Ce chapitre a été publié dans la revue Experientia Supplementum en, 2016.

, AMP-activated Protein Kinase, pp.153-177

, Neurodegenerative diseases including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and

A. Adp and . Sanders, AMPK is a heterotrimer composed of one ?, ? and y subunits, often referred to as a master energy sensor. Indeed, AMPK possesses on its regulatory ? subunit four CBS (cystathionine-beta-synthase) domains which are binding sites for adenine nucleotides. Three of these sites can bind AMP, Amyotrophic lateral sclerosis (ALS) are characterized by the progressive degeneration of nerve cells eventually leading to dementia. While these disorders affect different neuronal populations they share in common several features. For instance, they are characterized by the presence in degenerating neurons of protein aggregates that likely result from defective clearance mechanisms including proteasomal dysfunction and lysosomal clearance, 2002.

. Li, On the opposite AMPK up-regulates energy producing pathways such as mitochondrial biogenesis through the activation of the PGC-1? (peroxisome proliferator-activated receptor-? coactivator 1?) pathway, (ACC1) and the expression of enzymes involved in fatty acid synthesis by inhibition of the lipogenic transcription factor sterol regulatory element-binding protein C1, 1999.

, Metabolic stress induces an increase of the AMP/ATP ratio that promotes AMP binding to the ? subunit of AMPK. This induces a conformational change that allows the phosphorylation of AMPK by LKB1. Once activated, AMPK triggers catabolic pathways and represses anabolic pathways in order to maintain energetic homeostasis. ROS: reactive oxygen species; CamKKII: Calcium/calmodulin kinase kinase II, Regulation of AMPK. AMPK is a metabolic sensor which is activated by different stresses, vol.1

, Parkinson's disease (PD)

. Verstraeten, While the majority of cases are sporadic, mutations in a number of genes were identified to be responsible for rare familial forms of the disease. These genes include SNCA (coding for ?-synuclein), Park2 (coding for the cytosolic E3 ubiquitin ligase Parkin), and PINK1 (coding for PTEN-induced kinase 1). In addition, genetic variants have been identified as PD risk alleles in LRRK2 (leucine-rich repeat kinase 2), SNCA, H1 haplotype of microtubule, PD is characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Pathological features include loss of dopaminergic neurons in the substantia nigra associated with Lewy bodies inclusions (Beitz, 1999.

, Environmental factors include exposure to environmental toxins (pesticides, herbicides and industrial chemicals), and drugs of abuse (Olanow and, 1999.

. Valente, Interestingly, many of these genetic and environmental factors are linked to mitochondrial function. For example, PINK1 is localized to the mitochondria where it exerts a protective role that is abolished by mutations, overall resulting in a cellular increased susceptibility to stress, 2004.

. Narendra, As for sporadic cases, a decrease in the activity of mitochondrial respiratory chain complex I was found in the substantia nigra of PD patient's brain (Schapira et al., 1990). Complex I was found to be functionally impaired i.e. oxydatively damaged and misassembled, addition, PINK1 was found to activate Parkin on impaired mitochondria, 2000.

. Jiang, AMPK activation was also reported in animal models of PD induced by intra-striatal injection of 6-hydroxydopamine (6-OHDA) or MPTP, AMPK deregulation was observed in the brain of PD patients where activated AMPK was found near the ream of Lewy bodies in the cytoplasm as opposed to control individuals where AMPK was mainly nuclear, 2010.

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, Annexe 3 : Article "AMP-activated protein kinase is essential for the maintenance of energy levels during synaptic activation, 2018.

, , vol.9, pp.1-13, 2018.

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, AMP-activated protein kinase is essential for the maintenance of energy levels during synaptic activation

C. Marinangeli, S. Didier, T. Ahmed, R. Caillerez, M. Domise et al.,