Date of this Version
8-8-2017
Document Type
Article
Abstract
Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson’s disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial fission Dynamin-Related Protein-1 (Drp1). We show here that mdivi-1 reduced neurodegeneration, α-syn aggregates and normalized motor function. Mechanistically, mdivi-1 reduced mitochondrial fragmentation, mitochondrial dysfunction and oxidative stress. These in vivo results support the negative role of mutant α-syn in mitochondrial function and indicate that mdivi-1 has a high therapeutic potential for PD.
Identifier
FIDC006504
Rights
by
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Bido, Simone; Soria, Federico N.; Fan, Rebecca Z.; Bezard, Erwan; and Tieu, Kim, "Mitochondrial division inhibitor-1 is neuroprotective in the A53T-α-synuclein rat model of Parkinson’s disease" (2017). Environmental Health Sciences. 14.
https://digitalcommons.fiu.edu/eoh_fac/14
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Comments
Originally published in Scientific Reports.