Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson's disease.
Neurobiol Aging
; 55: 33-37, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28407521
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Fenótipo
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Biogênese de Organelas
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Proteínas de Drosophila
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Cofator PQQ
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Fator B de Elongação Transcricional Positiva
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Modelos Animais de Doenças
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Drosophila
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Modelos Genéticos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2017
Tipo de documento:
Article