{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:41:53Z","timestamp":1790347313298,"version":"4.1.0"},"reference-count":240,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"publisher","award":["RGPIN-2022-04865"],"award-info":[{"award-number":["RGPIN-2022-04865"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"publisher","award":["RGPIN-2019-06666"],"award-info":[{"award-number":["RGPIN-2019-06666"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"publisher","award":["202109PJT-469649-BSA-CFEB-307470"],"award-info":[{"award-number":["202109PJT-469649-BSA-CFEB-307470"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Neurodegenerative disorders, such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s disease, due to their multifaced and complicated nature, remain uncurable and impose substantial financial and human burdens on society. Therefore, developing new innovative therapeutic strategies is vital. In this context, drug repurposing has emerged as a promising avenue to expedite the development of treatments for these challenging conditions. One particularly compelling target in this regard is the chaperone protein sigma-1 receptor (S1R), which has garnered significant attention for its neuroprotective properties. Interestingly, several medications, including fluvoxamine (an antidepressant), dextromethorphan (a cough suppressant), and amantadine (an antiviral), which were initially developed for unrelated indications, have shown encouraging results in neurodegenerative therapy through S1R activation. These findings suggest that existing drugs in pharmacopeias can play an essential role in alleviating neurodegenerative symptoms by modulating S1R, thereby offering a faster route and cost-effective path to clinical applications compared to the de novo development of entirely new compounds. Furthermore, as a synergistic benefit, combining S1R-targeting drugs with other therapeutic agents may also improve treatment efficacy. In this review, we highlight key repurposed drugs targeting S1R and explore their mechanisms of action, shedding light on their emerging therapeutic potential in the fight against neurodegeneration.<\/jats:p>","DOI":"10.3390\/ph18050700","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T06:18:51Z","timestamp":1746771531000},"page":"700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Repurposing Sigma-1 Receptor-Targeting Drugs for Therapeutic Advances in Neurodegenerative Disorders"],"prefix":"10.3390","volume":"18","author":[{"given":"Kiarash","family":"Eskandari","sequence":"first","affiliation":[{"name":"D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3X8, Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Pavillon des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara-Maude","family":"B\u00e9langer","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3X8, Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Pavillon des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-0368","authenticated-orcid":false,"given":"V\u00e9ronik","family":"Lachance","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3X8, Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Pavillon des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kourrich","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3X8, Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, Pavillon des Sciences Biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 141 Avenue du Pr\u00e9sident-Kennedy, Montreal, QC H2X 3Y7, Canada"},{"name":"Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","first-page":"65","article-title":"The biological function of the Huntingtin protein and its relevance to Huntington\u2019s Disease pathology","volume":"5","author":"Schulte","year":"2011","journal-title":"Curr. 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