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 α-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2255-2262 |
| Number of pages | 8 |
| Journal | Brain |
| Volume | 141 |
| Issue number | 8 |
| DOIs | |
| State | Published - Jan 1 2018 |
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ASJC Scopus subject areas
- Clinical Neurology
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Is Parkinson's disease a lysosomal disorder? / Klein, Andrés D.; Mazzulli, Joe.
In: Brain, Vol. 141, No. 8, 01.01.2018, p. 2255-2262.Research output: Contribution to journal › Article
TY - JOUR
T1 - Is Parkinson's disease a lysosomal disorder?
AU - Klein, Andrés D.
AU - Mazzulli, Joe
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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 α-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.
AB - 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 α-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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U2 - 10.1093/brain/awy147
DO - 10.1093/brain/awy147
M3 - Article
VL - 141
SP - 2255
EP - 2262
JO - Brain
JF - Brain
SN - 0006-8950
IS - 8
ER -