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Defective Autophagy in Parkinson’s Disease: Lessons from Genetics

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Abstract

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement disorder. Genetic studies over the past two decades have greatly advanced our understanding of the etiological basis of PD and elucidated pathways leading to neuronal degeneration. Recent studies have suggested that abnormal autophagy, a well conserved homeostatic process for protein and organelle turnover, may contribute to neurodegeneration in PD. Moreover, many of the proteins related to both autosomal dominant and autosomal recessive PD, such as α-synuclein, PINK1, Parkin, LRRK2, DJ-1, GBA, and ATPA13A2, are also involved in the regulation of autophagy. We propose that reduced autophagy enhances the accumulation of α-synuclein, other pathogenic proteins, and dysfunctional mitochondria in PD, leading to oxidative stress and neuronal death.

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Acknowledgments

This work was supported by grants from The National Basic Research Program of China (2011CB504102, 2012CB722407), National Natural Science Foundation of China (81371398), Natural Science Foundation (7131001), and Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality (IDHT20140514).

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Zhang, H., Duan, C. & Yang, H. Defective Autophagy in Parkinson’s Disease: Lessons from Genetics. Mol Neurobiol 51, 89–104 (2015). https://doi.org/10.1007/s12035-014-8787-5

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  • DOI: https://doi.org/10.1007/s12035-014-8787-5

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