| http://purl.uniprot.org/citations/19021916 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19021916 | http://www.w3.org/2000/01/rdf-schema#comment | "α-synuclein (α-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. α-syn mutations or amplifications are responsible for a subset of autosomal dominant familial PD cases, and overexpression causes neurodegeneration and motor disturbances in animals. To investigate mechanisms for α-syn accumulation and toxicity, we studied a mouse model of lysosomal enzyme cathepsin D (CD) deficiency, and found extensive accumulation of endogenous α-syn in neurons without overabundance of α-syn mRNA. In addition to impaired macroautophagy, CD deficiency reduced proteasome activity, suggesting an essential role for lysosomal CD function in regulating multiple proteolytic pathways that are important for α-syn metabolism. Conversely, CD overexpression reduces α-syn aggregation and is neuroprotective against α-syn overexpression-induced cell death in vitro. In a C. elegans model, CD deficiency exacerbates α-syn accumulation while its overexpression is protective against α-syn-induced dopaminergic neurodegeneration. Mutated CD with diminished enzymatic activity or overexpression of cathepsins B (CB) or L (CL) is not protective in the worm model, indicating a unique requirement for enzymatically active CD. Our data identify a conserved CD function in α-syn degradation and identify CD as a novel target for LB disease therapeutics."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.org/dc/terms/identifier | "doi:10.1186/1756-6606-1-17"xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Liang Q."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Lu Y."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Peng L."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Zhou Y."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Iwatsubo T."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Wilson S."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Uchiyama Y."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Schneider L."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Roth K.A."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Qiao L."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Parks R."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Caldwell G.A."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Caldwell K.A."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Standaert D.G."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Hamamichi S."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Crimmins S."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Yacoubian T.A."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Crabtree D."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Shacka J.J."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Walls K.C."xsd:string |
| http://purl.uniprot.org/citations/19021916 | http://purl.uniprot.org/core/author | "Xie Z.L."xsd:string |