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Reduction of RPT6/S8 (a Proteasome Component) and Proteasome Activity in the Cortex is Associated with Cognitive Impairment in Lewy Body Dementia

J Alzheimers Dis.. 2017; 
Alghamdi A,Vallortigara J,Howlett DR,Broadstock M,Hortobágyi T,Ballard C,Thomas AJ,O'Brien JT,Aarsland D,Attems J,Francis PT,Whitfield DR.
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... Western blotting was undertaken as previously described [30]. Briefly, crude brain homogenate was diluted 4:5 with 5x sample buffer (Genscript MB01015, USA), boiled for 5 minutes then stored at -20°C. Samples were loaded at 20μg/ml total protein on 10% SDS- ...

摘要

Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined. Furthermore, the main proteolytic-like (chymotrypsin- and PGPH-) activities ... More

关键词

Alzheimer’s disease; Parkinson’s disease with dementia; RPT6; amyloid-beta; cognitive impairment; dementia with Lewy bodies; tau; ubiquitin proteasome system