Cerebral accumulation of amyloid beta-peptide (A beta), which is produced from amyloid precursor protein (APP), is the primary cause of Alzheimer's disease (AD). Autophagy recycles cellular components and digests intracellular components including A beta. The Ca2+- and Mg2+-permeable transient receptor potential melastatin 7 (TRPM7) channel underlies the constitutive Ca2+ influx in some cells. Since we already reported that TRPM7 channel-mediated Ca2+ influx regulates basal autophagy, we hypothesize that the activation of TRPM7 channel could increase basal autophagy and consequently decrease A beta. In this study, we showed that naltriben (NTB), a specific TRPM7 channel activator, induced Ca2+ influx and activated autophagic signaling in neuroblastoma SH-SY5Y cells. NTB also promoted co-localization of LC3 and APP, and reduced A beta. Furthermore, we found that an early-onset familial AD-associated presenilin1 Delta E9 (PSI Delta E9) mutant cells had attenuated basal autophagy. NTB was able to recover autophagy and decrease A beta in PS1 Delta E9 cells. Our results show that the activating TRPM7 channel may prevent AD related A beta neuropathology via modulating Ca2+-regulated basal autophagy. (C) 2017 Elsevier Inc. All rights reserved.