Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson’s disease
Autor: | Adeline H. Basil, Chee-Hoe Ng, Sharon Philomena O'Neill, Fengwei Yu, Royston Tan, Kah-Leong Lim, Kian-Leong Goh, Liting Hang, Xiao-Dong Zhang |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Aging Parkinson's disease Ubiquitin-Protein Ligases Neuroscience(all) PQQ Cofactor Clinical Neurology Gene Expression Biology Mitochondrion AMP-Activated Protein Kinases Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Neuroprotection Parkin 03 medical and health sciences 0302 clinical medicine Genetic model medicine Gene silencing Animals Drosophila Proteins Positive Transcriptional Elongation Factor B Gene Silencing Molecular Targeted Therapy Genetics Organelle Biogenesis Models Genetic General Neuroscience Parkinson Disease medicine.disease Phenotype Disease Models Animal Ageing 030104 developmental biology Neuroprotective Agents Mitochondrial biogenesis Drosophila Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | Neurobiology of Aging. |
ISSN: | 0197-4580 |
DOI: | 10.1016/j.neurobiolaging.2017.03.017 |
Popis: | 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. |
Databáze: | OpenAIRE |
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