{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:25:57Z","timestamp":1793103957109,"version":"4.5.0"},"reference-count":184,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T00:00:00Z","timestamp":1679788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cognition Therapeutics, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013protein 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-\u03b2 and \u03b1-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\u2019s disease, \u03b1-synucleinopathies, and dry age-related macular degeneration.<\/jats:p>","DOI":"10.3390\/ijms24076251","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T04:05:40Z","timestamp":1679889940000},"page":"6251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Sigma-2 Receptors\u2014From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-3913","authenticated-orcid":false,"given":"Britney N.","family":"Lizama","sequence":"first","affiliation":[{"name":"Cognition Therapeutics, Inc., Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-6610","authenticated-orcid":false,"given":"Jennifer","family":"Kahle","sequence":"additional","affiliation":[{"name":"IHS International, San Diego, CA92130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Catalano","sequence":"additional","affiliation":[{"name":"Cognition Therapeutics, Inc., Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony O.","family":"Caggiano","sequence":"additional","affiliation":[{"name":"Cognition Therapeutics, Inc., Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grundman","sequence":"additional","affiliation":[{"name":"Global R&D Partners, LLC., San Diego, CA 92130, USA"},{"name":"Department of Neurosciences, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-1853","authenticated-orcid":false,"given":"Mary E.","family":"Hamby","sequence":"additional","affiliation":[{"name":"Cognition Therapeutics, Inc., Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A Single\u2013Cell Type Transcriptomics Map of Human Tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci. 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