Le peptide NFL-TBS.40-63 issu des neurofilaments : agent thérapeutique et outil de ciblage des cellules de glioblastome et des cellules souches neurales.

Abstract : In the laboratory, investigations on neurofilament biology and on their interactions with other cytoskeleton components showed tubulin-binding sites (TBS) on different intermediate filaments. Among the synthesized peptide corresponding to these sequences, the NFLTBS.40-63 peptide derived from the neurofilament light subunit (NFL), revealed in vitro and in vivo targeting properties and anti-tumour effect on glioblastoma cells, the most frequent and aggressive brain tumour, for which current treatments show very limited effects. The therapeutic value of this peptide is reinforced by its lower uptake and the lack of a major cytotoxic effect in healthy cells (astrocytes, neurons). Works in this thesis describe the uptake mechanisms of the NFL-TBS.40-63 peptide in glioblastoma cells, to better understand its selective internalization. Its specificaction on glioblastoma cells has been completed by the analysis of the peptide effects on the mitochondrial organization and function. Finally, we show that the peptide targets neural stem cells, which could be at the origin of glioblastoma, and serve as a therapeutic tool inseveral brain diseases, such as traumatic injuries and neurodegenerative diseases. Altogether these works indicate that this NFL-TBS.40-63 peptide is a promising tool for therapeutic strategies of glioblastoma. It can also target neural stem cells in order to develop new treatments for various brain disorders.
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Claire Lépinoux-Chambaud. Le peptide NFL-TBS.40-63 issu des neurofilaments : agent thérapeutique et outil de ciblage des cellules de glioblastome et des cellules souches neurales.. Médecine humaine et pathologie. Université d'Angers, 2014. Français. ⟨NNT : 2014ANGE0039⟩. ⟨tel-02284909⟩

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