Linked Life Data

16380264

Source:http://linkedlifedata.com/resource/pubmed/id/16380264

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-5-1
pubmed:abstractText
Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase the availability of free monomeric ubiquitin to the ubiquitin proteasome system (UPS) thus favoring protein degradation. Since mutations in the UCHL-1 gene, reducing UPS activity by 50%, have been reported in autosomal dominant PD, and UCHL-1 inhibition results in the formation of alpha-synuclein aggregates in mesencephalic cultured neurons, the present study was initiated to test UCHL-1 mRNA and protein levels in post-mortem frontal cortex (area 8) of PD and DLB cases, compared with age-matched controls. TaqMan PCR assays, and Western blots demonstrated down-regulation of UCHL-1 mRNA and UCHL-1 protein in the cerebral cortex in DLB (either in pure forms, not associated with Alzheimer disease: AD, and in common forms, with accompanying AD changes), but not in PD, when compared with age-matched controls. Interestingly, UCHL-1 mRNA and protein expressions were reduced in the medulla oblongata in the same PD cases. Moreover, UCHL-1 protein was decreased in the substantia nigra in cases with Lewy body pathology. UCHL-1 down-regulation was not associated with reduced protein levels of several proteasomal subunits, including 20SX, 20SY, 19S and 11Salpha. Yet UCHL-3 expression was reduced in the cerebral cortex of PD and DLB patients. Together, these observations show reduced UCHL-1 expression as a contributory factor in the abnormal protein aggregation in DLB, and points UCHL-1 as a putative therapeutic target in the treatment of DLB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0969-9961
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
265-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16380264-Aged, pubmed-meshheading:16380264-Aged, 80 and over, pubmed-meshheading:16380264-Alzheimer Disease, pubmed-meshheading:16380264-Brain, pubmed-meshheading:16380264-Cerebral Cortex, pubmed-meshheading:16380264-Down-Regulation, pubmed-meshheading:16380264-Female, pubmed-meshheading:16380264-Humans, pubmed-meshheading:16380264-Lewy Bodies, pubmed-meshheading:16380264-Lewy Body Disease, pubmed-meshheading:16380264-Male, pubmed-meshheading:16380264-Medulla Oblongata, pubmed-meshheading:16380264-Middle Aged, pubmed-meshheading:16380264-Neurons, pubmed-meshheading:16380264-Parkinson Disease, pubmed-meshheading:16380264-Proteasome Endopeptidase Complex, pubmed-meshheading:16380264-Protein Subunits, pubmed-meshheading:16380264-RNA, Messenger, pubmed-meshheading:16380264-Signal Transduction, pubmed-meshheading:16380264-Substantia Nigra, pubmed-meshheading:16380264-Ubiquitin, pubmed-meshheading:16380264-Ubiquitin Thiolesterase
pubmed:year
2006
pubmed:articleTitle
Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.
pubmed:affiliation
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't