Yeo, In Jun Lee, Min Jae Baek, Ahruem Miller, Zachary Bhattarai, Deepak Baek, Yu Mi Jeong, Hyun Jung Kim, Yun Kyung Kim, Dong-Eun Hong, Jin Tae Kim, Kyung Bo 2024-01-19T18:32:46Z 2024-01-19T18:32:46Z 2021-09-05 2019-12-05 2045-2322 https://pubs.kist.re.kr/handle/201004/119212 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-alpha or IFN-gamma. 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 beta (A beta) 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 subunitY, ameliorates cognitive impairments in AD mouse models without affecting A beta 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. English NATURE PUBLISHING GROUP NONSTEROIDAL ANTIINFLAMMATORY DRUGS PREVENTION TRIAL ADAPT NF-KAPPA-B AMYLOID-BETA MACULAR DEGENERATION IMMUNOPROTEASOME MICROGLIA PROTEIN BRAIN IMPAIRMENT A dual inhibitor of the proteasome catalytic subunits LMP2 and Y attenuates disease progression in mouse models of Alzheimer's disease Article 10.1038/s41598-019-54846-z 1 SCIENTIFIC REPORTS, v.9 SCIENTIFIC REPORTS 9 scie scopus 000501568700001 2-s2.0-85076184076 Multidisciplinary Sciences Science & Technology - Other Topics Article NONSTEROIDAL ANTIINFLAMMATORY DRUGS PREVENTION TRIAL ADAPT NF-KAPPA-B AMYLOID-BETA MACULAR DEGENERATION IMMUNOPROTEASOME MICROGLIA PROTEIN BRAIN IMPAIRMENT proteasome alzheimer&apos s disease LAMP2 inhibitor