| http://purl.uniprot.org/citations/26170293 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26170293 | http://www.w3.org/2000/01/rdf-schema#comment | "A cellular feature of Parkinson's disease is cytosolic accumulation and amyloid formation of α-synuclein (α-syn), implicating a misregulation or impairment of protein degradation pathways involving the proteasome and lysosome. Within lysosomes, cathepsin D (CtsD), an aspartyl protease, is suggested to be the main protease for α-syn clearance; however, the protease alone only generates amyloidogenic C terminal-truncated species (e.g., 1-94, 5-94), implying that other proteases and/or environmental factors are needed to facilitate degradation and to avoid α-syn aggregation in vivo. Using liquid chromatography-mass spectrometry, to our knowledge, we report the first peptide cleavage map of the lysosomal degradation process of α-syn. Studies of purified mouse brain and liver lysosomal extracts and individual human cathepsins demonstrate a direct involvement of cysteine cathepsin B (CtsB) and L (CtsL). Both CtsB and CtsL cleave α-syn within its amyloid region and circumvent fibril formation. For CtsD, only in the presence of anionic phospholipids can this protease cleave throughout the α-syn sequence, suggesting that phospholipids are crucial for its activity. Taken together, an interplay exists between α-syn conformation and cathepsin activity with CtsL as the most efficient under the conditions examined. Notably, we discovered that CtsL efficiently degrades α-syn amyloid fibrils, which by definition are resistant to broad spectrum proteases. This work implicates CtsB and CtsL as essential in α-syn lysosomal degradation, establishing groundwork to explore mechanisms to enhance their cellular activity and levels as a potential strategy for clearance of α-syn."xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1500937112"xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/author | "Lee J.C."xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/author | "McGlinchey R.P."xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/pages | "9322-9327"xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/title | "Cysteine cathepsins are essential in lysosomal degradation of alpha-synuclein."xsd:string |
| http://purl.uniprot.org/citations/26170293 | http://purl.uniprot.org/core/volume | "112"xsd:string |
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