RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/14722078http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14722078http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14722078http://www.w3.org/2000/01/rdf-schema#comment"Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases that occur either in relatively rare, familial forms or in common, sporadic forms. The genetic defects underlying several monogenic familial forms of AD and PD have recently been identified, however, the causes of other AD and PD cases, particularly sporadic cases, remain unclear. To gain insights into the pathogenic mechanisms involved in AD and PD, we used a proteomic approach to identify proteins with altered expression levels and/or oxidative modifications in idiopathic AD and PD brains. Here, we report that the protein level of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), a neuronal de-ubiquitinating enzyme whose mutation has been linked to an early-onset familial PD, is down-regulated in idiopathic PD as well as AD brains. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified three human brain UCH-L1 isoforms, a full-length form and two amino-terminally truncated forms. Our proteomic analyses reveal that the full-length UCH-L1 is a major target of oxidative damage in AD and PD brains, which is extensively modified by carbonyl formation, methionine oxidation, and cysteine oxidation. Furthermore, immunohistochemical studies show that prominent UCH-L1 immunostaining is associated with neurofibrillary tangles and that the level of soluble UCH-L1 protein is inversely proportional to the number of tangles in AD brains. Together, these results provide evidence supporting a direct link between oxidative damage to the neuronal ubiquitination/de-ubiquitination machinery and the pathogenesis of sporadic AD and PD."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m314124200"xsd:string
http://purl.uniprot.org/citations/14722078http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m314124200"xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Weintraub S.T."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Weintraub S.T."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Choi J."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Choi J."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Levey A.I."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Levey A.I."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Gearing M."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Gearing M."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Chin L.-S."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Chin L.-S."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Rees H.D."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/author"Rees H.D."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/pages"13256-13264"xsd:string
http://purl.uniprot.org/citations/14722078http://purl.uniprot.org/core/pages"13256-13264"xsd:string