beta-Amyloid (A beta) plaque in the brains of patients with Alzheimer's disease (AD) is mainly caused by impaired clearance of A beta 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 A beta phagocytosis. This study found that TLQP-21, which is cleaved from VGF (VGF nerve growth factor inducible) precursor protein, enhanced A beta phagocytosis and degradation by microglial BV2 cells. TLQP-21 also improved microglial phagocytic activity and promoted fibrillar amyloid-beta (fA beta) uptake by microglial BV2 cells via a C3AR1-dependent mechanism. Moreover, TLQP-21 stimulated A beta degradation by enhancing lysosome activity, thereby enhancing fA beta clearance. These results suggest that treatment with TLQP-21 may be a novel therapeutic strategy to efficiently enhance microglial A beta clearance in AD. (C) 2020 Elsevier Inc. All rights reserved.