Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson's disease

NEUROBIOLOGY OF AGING

卷:55

Article

Ng, Chee-Hoe¹  Basil, Adeline H.¹  Hang, Liting^1,2  Tan, Royston¹  Goh, Kian-Leong^1,2  O'Neill, Sharon²  Zhang, Xiaodong²  Yu, Fengwei³  Lim, Kah-Leong^1,2,4 

[1] Natl Neurosci Inst, Dept Res, Singapore, Singapore

[2] Duke NUS Med Sch, Neurosci & Behav Disorders Program, Singapore, Singapore

[3] Temasek Life Sci Lab, Singapore, Singapore

[4] Natl Univ Singapore, Dept Physiol, Singapore, Singapore

关键词: Parkinson's disease;    Mitochondria;    PGC-1 alpha;    Neuroprotection;    Parkin;   

DOI  :  10.1016/j.neurobiolaging.2017.03.017

来源: Elsevier

【 摘 要 】

Despite intensive research, the etiology of Parkinson's disease (PD) remains poorly understood and the disease remains incurable. However, compelling evidence gathered over decades of research strongly support a role for mitochondrial dysfunction in PD pathogenesis. Related to this, PGC-1 alpha, a key regulator of mitochondrial biogenesis, has recently been proposed to be an attractive target for intervention in PD. Here, we showed that silencing of expression of the Drosophila PGC-1 alpha ortholog spargel results in PD-related phenotypes in flies and also seem to negate the effects of AMPK activation, which we have previously demonstrated to be neuroprotective, that is, AMPK-mediated neuroprotection appears to require PGC-1 alpha. Importantly, we further showed that genetic or pharmacological activation of the Drosophila PGC-1 alpha ortholog spargel is sufficient to rescue the disease phenotypes of Parkin and LRRK2 genetic fly models of PD, thus supporting the proposed use of PGC-1 alpha-related strategies for neuroprotection in PD. (C) 2017 National Neuroscience Institute. Published by Elsevier Inc.

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