{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:19:00Z","timestamp":1790536740427,"version":"4.1.0"},"reference-count":125,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Development of Science and Technology of Jilin Province","award":["YDZJ202601ZYTS314"],"award-info":[{"award-number":["YDZJ202601ZYTS314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sympathetic nervous system (SNS) imbalance is a common pathological basis for cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. This review focuses on these diseases, analyzing two core mechanisms: excessive sympathetic excitation induced by endoplasmic reticulum stress (ERS) or autophagy dysfunction in key central nuclei (e.g., hypothalamus, rostral ventrolateral medulla); and ERS\/autophagy abnormalities in peripheral target organs caused by chronic SNS overactivation. Existing studies confirm that chronic SNS overactivation promotes peripheral metabolic overload via sustained catecholamine release, inducing persistent ERS and disrupting the protective unfolded protein response (UPR)\u2013autophagy network, ultimately leading to cell apoptosis, inflammation, and fibrosis. Notably, central ERS or autophagy dysfunction further perturbs autonomic homeostasis, exacerbating sympathetic overexcitation. This review systematically elaborates on SNS overactivation as a critical bridge mediating UPR\u2013autophagy network dysregulation in central and peripheral tissues, and explores therapeutic prospects of targeting key nodes (e.g., chemical chaperones, specific UPR modulators, nanomedicine), providing a theoretical basis for basic research and clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27031282","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives"],"prefix":"10.3390","volume":"27","author":[{"given":"Bo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0058-6219","authenticated-orcid":false,"given":"Renjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1159\/000544971","article-title":"When Proteins Go Berserk: The Unfolded Protein Response and ER Stress","volume":"149","author":"Meiseles","year":"2025","journal-title":"Nephron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1111\/febs.70113","article-title":"Glucose sensing and the unfolded protein response","volume":"292","author":"Chevet","year":"2025","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e202405060","DOI":"10.1083\/jcb.202405060","article-title":"Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity","volume":"224","author":"Huo","year":"2025","journal-title":"J. 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