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
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
Externí odkaz: