The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer’s
| Autor: | Mani Iyer Prasanth, Tewin Tencomnao, Dicson Sheeja Malar, James M. Brimson |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Thiophenes 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Drug Discovery Autophagy Animals Humans Receptors sigma Spiro Compounds Molecular Targeted Therapy Furans Receptor Lipid raft Pharmacology Sigma-1 receptor Chemistry Mechanism (biology) Catabolism Maleates Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Thiazolidines Molecular Medicine Function (biology) |
| Zdroj: | Expert Opinion on Therapeutic Targets. 25:401-414 |
| ISSN: | 1744-7631 1472-8222 |
| DOI: | 10.1080/14728222.2021.1939681 |
| Popis: | 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 (σ-1R) is a chaperone protein involved in signal transduction, neurite outgrowth, and plasticity, improving memory, and neuroprotection. Recent evidence shows that σ-1R can promote autophagy. Autophagy activation by the σ-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 σ-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.This review provides insight into the current understanding of σ-1R functions related to autophagy and their role in alleviating AD.We propose a mechanism through which the activation of σ-1R and autophagy could alter amyloid precursor protein processing to inhibit amyloid-β 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 σ-1R and autophagy activation. We suggest that future studies investigate the link between autophagy the σ-1R and AD. |
| Databáze: | OpenAIRE |
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