Is Parkinson's disease a lysosomal disorder?
Date
2018
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Article
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Abstract
Common forms of Parkinson’s disease have long been described as idiopathic, with no single penetrant genetic factor capable of influencing disease aetiology. Recent genetic studies indicate a clear association of variants within several lysosomal genes as risk
factors for idiopathic Parkinson’s disease. The emergence of novel variants suggest that the aetiology of idiopathic Parkinson’s disease may be explained by the interaction of several partially penetrant mutations that, while seemingly complex, all appear to
converge on cellular clearance pathways. These newly evolving data are consistent with mechanistic studies linking a-synuclein toxicity to lysosomal abnormalities, and indicate that idiopathic Parkinson’s disease resembles features of Mendelian lysosomal
storage disorders at a genetic and biochemical level. These findings offer novel pathways to exploit for the development of diseasealtering therapies for idiopathic Parkinson’s disease that target specific components of the lysosomal system.
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Citation
Klein AD, Mazzulli JR. Is Parkinson's disease a lysosomal disorder? Brain. 2018 Aug 1;141(8):2255-2262. doi: 10.1093/brain/awy147.
Keywords
Neurodegeneration, Alpha-synuclein, Lysosomal storage disease, Protein trafficking, Autophagy