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Acute inflammation destroys OSNs, causing hyposmia and anosmia, but activates basal cells. Manipulation of signaling pathways to promote basal cell proliferation and neuroregeneration would reveal novel therapeutic targets for smell deficits. We found that ciliary neurotrophic factor (CNTF) from horizontal basal cells (HBCs, quiescent stem cells) promotes neuroregeneration and functional recovery following methimazole-induced acute injury. Moreover, inhibition of focal adhesion kinase (FAK) upregulates CNTF in na\u00efve OE. Here, we show that the small molecule FAK inhibitor increased CNTF expression in cultured primary HBCs isolated from methimazole-treated mice. Although methimazole-induced CNTF did not seem to be through FAK signaling, inducible cre-lox knockout of FAK in HBCs in mice further increased CNTF expression, as well as Mash1, a marker for globose basal cells (GBCs, neuronal progenitors), and GBC proliferation. Moreover, intranasal aspiration, but not systemic treatment, of a water-soluble pharmacological FAK inhibitor (FAK14) 3\u2009days following methimazole, dose-dependently increased CNTF and Mash1 expression, and GBC proliferation. Intranasal FAK14 also enhanced methimazole-induced regeneration of new OSNs in CNTF+\/+, but not in CNTF\u2212\/\u2212, mice, demonstrating that FAK14 boosts neuroregeneration through additional CNTF following acute inflammation. Finally, intranasal FAK14 instillation following methimazole improved the functional recovery of smell. This study identifies the therapeutic potential of intranasal application of FAK inhibitors to enhance olfactory neuroregeneration and function following injury.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag011","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T12:52:57Z","timestamp":1772283177000},"source":"Crossref","is-referenced-by-count":0,"title":["FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF"],"prefix":"10.1093","volume":"44","author":[{"given":"Derek","family":"Cox","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeden","family":"Pyburn","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morning Dove","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego J","family":"Rodriguez-Gil","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo","family":"Hagg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9693-0012","authenticated-orcid":false,"given":"Cuihong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN 37614,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"2026040913573395900_sxag011-B1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/0166-2236(90)90017-5","article-title":"Olfactory neurogenesis: genetic or environmental controls?","volume":"13","author":"Farbman","year":"1990","journal-title":"Trends Neurosci"},{"key":"2026040913573395900_sxag011-B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF01206454","article-title":"Neurogenesis and neuron regeneration in the olfactory system of mammals. 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