Dipeptidyl Vinyl Sulfone as a Novel Chemical Tool to Inhibit HMGB1/NLRP3-Inflammasome and Inflamma-miRs in Aβ-Mediated Microglial Inflammation
Rapid microglial activation and associated inflammatory pathways contribute to immune-defense and tissue repair in the central nervous system (CNS). However, persistent activation of these cells will ultimately result in vast production of pro-inflammatory mediators and other neurotoxic factors, which may induce neuronal damage and contribute to chronic neurodegenerative diseases, as Alzheimer’s disease (AD). Therefore, small molecules with immunomodulatory effects on microglia may be considered as potential tools to counteract their proinflammatory phenotype and neuroimmune dysregulation in such disorders. Indeed, reducing amyloid-β (Aβ)-induced microglia activation is believed to be effective in treating AD. In this study, we investigated whether dipeptidyl vinyl sulfone (VS) was able to attenuate Aβ-mediated inflammatory response using a mouse microglial (N9) cell line and a solution containing a mixture of Aβ aggregates. We show that low levels of VS are able to prevent cell death while reducing microglia phagocytosis upon Aβ treatment. VS also suppressed Aβ-induced expression of inflammatory mediators in microglia, such as matrix metalloproteinase (MMP)-2 and MMP-9, as well as high-mobility group box protein-1 (HMGB1), nod-like receptor protein 3 (NLRP3)-inflammasome, and interleukin (IL)-1β. Interestingly, increased expression of the two critical inflammation-related microRNAs (miR)-155 and miR-146a in microglia upon Aβ treatment was also prevented by VS coincubation. Taken together, VS emerges as a potential new therapeutic strategy worthy of further investigation in improved cellular and animal models of AD. Graphic Abstract ACS Electronic Supporting Info
- 원문이 없습니다.
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.
- 이 논문과 함께 출판된 논문 + 더보기