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

Published

Journal Article

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-1α, 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-1α 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-1α. Importantly, we further showed that genetic or pharmacological activation of the Drosophila PGC-1α 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-1α-related strategies for neuroprotection in PD.

Full Text

Duke Authors

Cited Authors

  • Ng, C-H; Basil, AH; Hang, L; Tan, R; Goh, K-L; O'Neill, S; Zhang, X; Yu, F; Lim, K-L

Published Date

  • July 2017

Published In

Volume / Issue

  • 55 /

Start / End Page

  • 33 - 37

PubMed ID

  • 28407521

Pubmed Central ID

  • 28407521

Electronic International Standard Serial Number (EISSN)

  • 1558-1497

International Standard Serial Number (ISSN)

  • 0197-4580

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2017.03.017

Language

  • eng