The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer's

摘要

Introduction Autophagy is a cellular catabolic mechanism that helps clear damaged cellular components and is essential for normal cellular and tissue function. The sigma-1 receptor (sigma-1R) is a chaperone protein involved in signal transduction, neurite outgrowth, and plasticity, improving memory, and neuroprotection. Recent evidence shows that sigma-1R can promote autophagy. Autophagy activation by the sigma-1Rs along with other neuroprotective effects makes it an interesting target for the treatment of Alzheimer's disease. AF710B, T-817 MA, and ANAVEX2-73 are some of the sigma-1R agonists which have shown promising results and have entered clinical trials. These molecules have also been found to induce autophagy and show cytoprotective effects in cellular models. Areas covered This review provides insight into the current understanding of sigma-1R functions related to autophagy and their role in alleviating AD. Expert Opinion We propose a mechanism through which the activation of sigma-1R and autophagy could alter amyloid precursor protein processing to inhibit amyloid-beta production by reconstituting cholesterol and gangliosides in the lipid raft to offer neuroprotection against AD. Future AD treatment could involve the combined targeting of the sigma-1R and autophagy activation. We suggest that future studies investigate the link between autophagy the sigma-1R and AD.