TLQP-21의 미세아교세포 C3a 수용체 (C3AR1)를 매개로 한 베타-아밀로이드 섭식의 촉진

Abstract

In Alzheimer's disease (AD), β-Amyloid (Aβ) plaque is caused by overproduction and impaired clearance of Aβ by glial cells including microglia and astrocytes. Because microglia play an important protective role in the central nervous system (CNS), there have been many tries to find effective agents for improving microglial Aβ phagocytosis. VGF (VGF nerve growth factor inducible), the neuropeptide belongs to granin family, is a precursor protein that cleaved to several VGF-derived peptides by proteolytic enzymes and TLQP-21 increases intracellular Ca2+ levels on microglia, suggesting that TLQP-21 can modulate microglial function and pathogenesis of AD or not is unclear. In this study, it's confirmed that TLQP-21 improves phagocytosis and promotes fAβ uptake via C3AR1-dependent mechanism on microglial BV2 cell lines. TLQP-21 also stimulates Aβ degradation by enhancing the function of autophagosome and lysosome, and consequently enhances the ability of fAβ clearance on microglia. Despite of these effects, TLQP-21 did not affect inflammation-related cytokines release. These results suggest that TLQP-21 induced microglial Aβ clearance and TLQP-21 may be novel potential therapeutics for AD.