{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:42:01Z","timestamp":1790347321895,"version":"4.1.0"},"reference-count":232,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.<\/jats:p>","DOI":"10.3390\/ijms24031997","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"1997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases"],"prefix":"10.3390","volume":"24","author":[{"given":"Francisco Javier","family":"Munguia-Galaviz","sequence":"first","affiliation":[{"name":"Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Division de Ciencias de la Salud, Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzman 49000, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra Guillermina","family":"Miranda-Diaz","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Alejandro","family":"Cardenas-Sosa","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9136-8382","authenticated-orcid":false,"given":"Raquel","family":"Echavarria","sequence":"additional","affiliation":[{"name":"CONACYT-Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1038\/cdd.2016.91","article-title":"Alternative splicing and cell survival: From tissue homeostasis to disease","volume":"23","author":"Paronetto","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_2","first-page":"517","article-title":"The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog","volume":"197","author":"Martin","year":"1976","journal-title":"J. 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