A dual inhibitor of the proteasome catalytic subunits LMP2 andY attenuates disease progression in mouse models of Alzheimer’s disease

Title
A dual inhibitor of the proteasome catalytic subunits LMP2 andY attenuates disease progression in mouse models of Alzheimer’s disease
Authors
김윤경정현정여인준이민재백아름Zachary Miller김동은홍진태김경보Deepak BhattaraiYu Mi Baek
Keywords
proteasome; alzheimer's disease; LAMP2; inhibitor
Issue Date
2019-12
Publisher
Scientific Reports
Citation
VOL 9, 18393
Abstract
The immunoproteasome (iP) is a variant of the constitutive proteasome (cP) that is abundantly expressed in immune cells which can also be induced in somatic cells by cytokines such as TNF-α or IFN-γ. Accumulating evidence support that the iP is closely linked to multiple facets of inflammatory response, eventually leading to the development of several iP inhibitors as potential therapeutic agents for autoimmune diseases. Recent studies also found that the iP is upregulated in reactive glial cells surrounding amyloid β (Aβ) deposits in brains of Alzheimer’s disease (AD) patients, but the role it plays in the pathogenesis of AD remains unclear. In this study, we investigated the effects of several proteasome inhibitors on cognitive function in AD mouse models and found that YU102, a dual inhibitor of the iP catalytic subunit LMP2 and the cP catalytic subunit Y, ameliorates cognitive impairments in AD mouse models without affecting Aβ deposition. The data obtained from our investigation revealed that YU102 suppresses the secretion of inflammatory cytokines from microglial cells. Overall, this study indicates that there may exist a potential link between LMP2/Y and microglia-mediated neuroinflammation and that inhibition of these subunits may offer a new therapeutic strategy for AD.
URI
http://pubs.kist.re.kr/handle/201004/71954
ISSN
2045-2322
Appears in Collections:
KIST Publication > Article
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