AMP Kinase Activation Mitigates Dopaminergic Dysfunction and Mitochondrial Abnormalities inDrosophilaModels of Parkinson's Disease

• DOI: 10.1523/jneurosci.0499-12.2012
• Publication Date: 2012-10-10T18:54:32Z
• Authors: Chee-Hoe Ng; Melissa S. H. Guan; Cherlyn Koh; Xuezhi Ouyang; Fengwei Yu; Eng-King Tan; Sharon Philomena ...; Xiaodong Zhang; Jongkyeong Chung; Kah-Leong Lim
• Keywords: LRRK2; PINK1

Mutations in parkin and LRRK2 together account for the majority of familial Parkinson's disease (PD) cases. Interestingly, recent evidence implicates involvement mitochondrial homeostasis. Supporting this, we show here by means Drosophila model system that, like parkin, mutations induce pathology flies when expressed their flight muscles, toxic effects which can be rescued coexpression. When specifically fly dopaminergic neurons, mutant results appearance significantly enlarged mitochondria, a phenotype that also Importantly, identified this study epigallocatechin gallate (EGCG), green tea-derived catechin, acts as potent suppressor dysfunction both parkin-null flies. Notably, protective EGCG are abolished AMP-activated protein kinase (AMPK) is genetically inactivated, suggesting EGCG-mediated neuroprotection requires AMPK. Consistent with direct pharmacological or genetic activation AMPK reproduces EGCG's effects. Conversely, loss activity exacerbates neuronal associated phenotypes LRRK Together, our suggest relevance mitochondrial-associated pathway parkin-related pathogenesis, may represent potential therapeutic strategy these forms PD.