Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-8-6
pubmed:abstractText
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed abundantly in neurons and has been reported to be a major target of oxidative/carbonyl damage associated with sporadic Parkinson's disease (PD). The I93M mutation in UCH-L1 is also associated with familial PD. We recently reported that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy (CMA), and Hsc70 and Hsp90, both of which can function as components of the CMA pathway. We found that the levels of these interactions were aberrantly increased by the I93M mutation, and that expression of I93M UCH-L1 in cells induced the CMA inhibition-associated increase in the amount of alpha-synuclein, a risk factor for PD. The interactions of UCH-L1 with LAMP-2A, Hsc70 and Hsp90 were also abnormally enhanced by carbonyl modification of UCH-L1. We propose that aberrant interactions of UCH-L1 variants with CMA machinery, at least partly, underlie the pathogenesis of I93M UCH-L1-associated PD, and possibly of sporadic PD. Our findings may provide novel insights into the links between familial and sporadic PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1554-8635
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
827-9
pubmed:dateRevised
2011-6-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Insights into links between familial and sporadic Parkinson's disease: physical relationship between UCH-L1 variants and chaperone-mediated autophagy.
pubmed:affiliation
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. kabuta@ncnp.go.jp
pubmed:publicationType
Journal Article