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

Expert Opinion on Therapeutic Targets
Mani Iyer PrasanthJames Michael Brimson

Abstract

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 th...Continue Reading

References

Mar 1, 1992·Trends in Pharmacological Sciences·R QuirionD P Taylor
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M HannerH Glossmann
Dec 13, 1996·Biochemical and Biophysical Research Communications·R KekudaV Ganapathy
Nov 19, 1997·The Medical Journal of Australia·A F Jorm
Jan 13, 1998·Biochemical and Biophysical Research Communications·P SethV Ganapathy
Apr 16, 1998·European Journal of Pharmacology·M TatsumiE Richelson
Mar 1, 2002·The American Journal of Psychiatry·Yvette I ShelineAbraham Z Snyder
Jul 30, 2003·Neurobiology of Aging·Kazunori KawamuraKiichi Ishiwata
Nov 19, 2003·The European Journal of Neuroscience·Francina LangaLluís Montoliu
Oct 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Teruo Hayashi, Tsung-Ping Su
Mar 9, 2005·Journal of Neuropathology and Experimental Neurology·Ralph A NixonAna Maria Cuervo
Apr 28, 2005·Current Biology : CB·Daniel J Klionsky
Nov 30, 2005·Annals of Neurology·Scott A SmallTae-Wan Kim
Dec 24, 2005·Human Molecular Genetics·Zdenek BergerDavid C Rubinsztein
Jul 29, 2006·Autophagy·Ana Maria CuervoAlexei Terman
Sep 20, 2006·The Journal of Cell Biology·György CsordásGyörgy Hajnóczky
Jan 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascale N LacorWilliam L Klein
Aug 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Masaaki KomatsuZhenyu Yue
Nov 23, 2007·Journal of Cell Science·Ralph A Nixon
Dec 7, 2007·Cancer Research·Christopher P PalmerEbru Aydar
Mar 29, 2008·Current Neuropharmacology·T Hayashi, Tp Su
Apr 22, 2008·Methods in Molecular Biology·Isei TanidaEiki Kominami
May 24, 2008·Annals of Nuclear Medicine·Masahiro MishinaKiichi Ishiwata
Jul 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry BolandRalph A Nixon

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Citations

Jun 29, 2021·Expert Opinion on Therapeutic Targets·Mani Iyer PrasanthJames Michael Brimson

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