Web of Science: 39 cites, Scopus: 43 cites, Google Scholar: cites,
Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.
Barrachina, Marta (Hospital Universitari de Bellvitge. Servei Anatomia Patològica)
Castaño, Esther (Universitat de Barcelona. Unitat de Biologia)
Dalfo Capella, Esther (Universitat Autònoma de Barcelona. Departament de Biologia i Bioquímica Molecular)
Maes, Tamara (Parc Científic de Barcelona. ORYZON Genomics)
Buesa, Carlos (Universitat de Barcelona. Departament de Biologia i Bioquímica Molecular)
Ferrer, Isidro (Universitat de Barcelona. Unitat de Neuropatologia Experimental)

Data: 2006
Resum: Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal α-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 a-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 agematched 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 11Sα. 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.
Drets: Tots els drets reservats.
Llengua: Anglès.
Document: article ; recerca ; publishedVersion
Matèria: Dementia with Lewy Bodies ; Parkinson's disease ; UCHL ; Proteasome ; A-synuclein
Publicat a: Neurobiology of disease, Vol. 22, Num. 2 (2006) , p. 265-73, ISSN 0969-9961

DOI: 10.1016/j.nbd.2005.11.005

9 p, 525.8 KB

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