ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, South Korea.
Department of Brain Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Biochem Biophys Res Commun. 2020 Apr 9;524(3):764-771. doi: 10.1016/j.bbrc.2020.01.111. Epub 2020 Feb 7.
β-Amyloid (Aβ) plaque in the brains of patients with Alzheimer's disease (AD) is mainly caused by impaired clearance of Aβ by glial cells, including microglia and astrocytes. Because microglia play an important protective role in the central nervous system, many efforts have been made to identify agents that effectively improve microglial Aβ phagocytosis. This study found that TLQP-21, which is cleaved from VGF (VGF nerve growth factor inducible) precursor protein, enhanced Aβ phagocytosis and degradation by microglial BV2 cells. TLQP-21 also improved microglial phagocytic activity and promoted fibrillar amyloid-β (fAβ) uptake by microglial BV2 cells via a C3AR1-dependent mechanism. Moreover, TLQP-21 stimulated Aβ degradation by enhancing lysosome activity, thereby enhancing fAβ clearance. These results suggest that treatment with TLQP-21 may be a novel therapeutic strategy to efficiently enhance microglial Aβ clearance in AD.
β-淀粉样蛋白（Aβ）斑块存在于阿尔茨海默病（AD）患者的大脑中，主要是由于神经胶质细胞（包括小胶质细胞和星形胶质细胞）清除 Aβ的功能受损所致。由于小胶质细胞在中枢神经系统中发挥着重要的保护作用，因此人们已经做出了许多努力来寻找能够有效提高小胶质细胞 Aβ吞噬作用的药物。本研究发现，TLQP-21 是从 VGF（神经生长因子诱导的 VGF）前体蛋白中切割而来的，可增强小胶质细胞 BV2 细胞对 Aβ的吞噬和降解。TLQP-21 还通过 C3AR1 依赖的机制提高了小胶质细胞的吞噬活性，并促进了纤维状淀粉样-β（fAβ）的摄取。此外，TLQP-21 通过增强溶酶体活性来刺激 Aβ降解，从而增强 fAβ的清除。这些结果表明，TLQP-21 的治疗可能是一种有效的治疗策略，可以有效地增强 AD 中小胶质细胞对 Aβ的清除。
