Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.

摘要: Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein ubiquitin in protein aggregates conforming neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase availability free monomeric proteasome system (UPS) thus favoring degradation. Since mutations UCHL-1 gene, reducing UPS activity 50%, have been reported autosomal dominant PD, inhibition results formation mesencephalic cultured neurons, present study was initiated test mRNA levels post-mortem frontal cortex (area 8) PD DLB cases, compared age-matched controls. TaqMan PCR assays, Western blots demonstrated down-regulation cerebral (either pure forms, not associated Alzheimer disease: AD, common accompanying AD changes), but when Interestingly, expressions were reduced medulla oblongata same cases. Moreover, decreased substantia nigra cases body pathology. several proteasomal subunits, including 20SX, 20SY, 19S 11Salpha. Yet UCHL-3 expression patients. Together, these observations show as a contributory factor aggregation DLB, points putative therapeutic target treatment DLB.