{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:27:22Z","timestamp":1791502042766,"version":"4.3.4"},"reference-count":201,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Neurodegenerative diseases (NDDs) are a major public health concern characterized by the progressive loss of neurons, ultimately leading to neuronal death and causing a sustained decline in brain function or physical motor abilities. Major examples include Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD). Currently, NDDs lack effective curative methods, and their pathological process primarily involves misfolded protein aggregation, oxidative stress, and neuroinflammation. The Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) signaling pathway, as a central hub for cytokine signaling, has recently been found to play a key role in neuroinflammation and immune regulation in NDDs. This review systematically elucidates the core mechanisms of the JAK\/STAT pathway in NDDs, including the regulation of microglial and astrocytic reactivity, the impact on blood\u2013brain barrier integrity, and involvement in energy metabolism abnormalities. On this basis, we have reviewed and evaluated various therapeutic strategies targeting this pathway, focusing on small-molecule JAK inhibitors such as baricitinib and tofacitinib, and have analyzed their mechanisms of action, preclinical efficacy, and potential side effects. In addition, this article provides a forward-looking perspective on the future research directions of the JAK\/STAT pathway from the perspective of anti-neuroinflammation to promote neuroregeneration therapy, aiming to offer theoretical references and new ideas for the clinical translational research of this pathway.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1880374","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:13Z","timestamp":1783661953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["JAK\/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives"],"prefix":"10.3389","volume":"18","author":[{"given":"Hai-Xia","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]},{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Wei","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]},{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Nan","family":"Bao","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Lao","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yu","family":"Ji","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Cui","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]},{"name":"Dalian Key Laboratory for Nuclear Receptors in Major Metabolic Diseases","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Wen","family":"Ren","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]},{"name":"Dalian Key Laboratory for Nuclear Receptors in Major Metabolic Diseases","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Lin","family":"Luan","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University","place":["Dalian, China"]},{"name":"Dalian Key Laboratory for Nuclear Receptors in Major Metabolic Diseases","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1007\/s00210-018-1523-3","article-title":"Modulation of brain ace and ACE2 may be a promising protective strategy against cerebral ischemia\/reperfusion injury: an experimental trial in rats","volume":"391","author":"Abdel-Fattah","year":"2018","journal-title":"Naunyn Schmiedeberg's Arch. 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