Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases
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Published:2023-03-26
Issue:7
Volume:24
Page:6251
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Lizama Britney N.1ORCID, Kahle Jennifer2ORCID, Catalano Susan M.1, Caggiano Anthony O.1, Grundman Michael34, Hamby Mary E.1ORCID
Affiliation:
1. Cognition Therapeutics, Inc., Pittsburgh, PA 15203, USA 2. IHS International, San Diego, CA92130, USA 3. Global R&D Partners, LLC., San Diego, CA 92130, USA 4. Department of Neurosciences, University of California, San Diego, CA 92093, USA
Abstract
There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related degenerative diseases of the central nervous system. The sigma-2 receptor (S2R), encoded by TMEM97, is expressed in brain and retinal cells, and regulates cell functions via its co-receptor progesterone receptor membrane component 1 (PGRMC1), and through other protein–protein interactions. Studies describing functions of S2R involve the manipulation of expression or pharmacological modulation using exogenous small-molecule ligands. These studies demonstrate that S2R modulates key pathways involved in age-related diseases including autophagy, trafficking, oxidative stress, and amyloid-β and α-synuclein toxicity. Furthermore, S2R modulation can ameliorate functional deficits in cell-based and animal models of disease. This review summarizes the current evidence-based understanding of S2R biology and function, and its potential as a therapeutic target for age-related degenerative diseases of the central nervous system, including Alzheimer’s disease, α-synucleinopathies, and dry age-related macular degeneration.
Funder
Cognition Therapeutics, Inc.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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