Journal
NEUROSCIENCE LETTERS
Volume 627, Issue -, Pages 36-41Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2016.05.039
Keywords
Parkinson's disease; ER stress response; ATF4; Alpha-synuclein; AAV
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Funding
- M. J. Fox Foundation
- VSRC Core Grant [P30 EY003039]
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Activating transcription factor 4 (ATF4) is a member of the PERK signaling pathway, which directly binds endoplasmic reticulum stress target genes and plays a crucial role in both adaptations to stress and activation of apoptosis. Previous publications demonstrated conflicting evidence on the role of ATF4 in the pathogenesis of neurodegenerative disorders. In this study, we used recombinant adeno-associate virus (rAAV)-mediated gene transfer to investigate if the sustained up-regulation of ATF4 launches a pro-survival or pro-death trend in the dopamine (DA) cells of the substantia nigra pars compacta in a rat model of Parkinson-like neurodegeneration induced by human alpha-synuclein (alpha S) overexpression. We showed that ATF4 does not protect nigral DA neurons against an alpha S-induced pathology. Moreover, the rAAV-mediated overexpression of ATF4 resulted in severe nigra-striatal degeneration via activation of caspases 3/7. Published by Elsevier Ireland Ltd.
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