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Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively counter the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood\u2013testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood\u2013testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.<\/jats:p>","DOI":"10.3390\/cells13232016","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T03:44:47Z","timestamp":1733456687000},"page":"2016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Riluzole Reverses Blood\u2013Testis Barrier Loss to Rescue Chemotherapy\u2013Induced Male Infertility by Binding to TRPC"],"prefix":"10.3390","volume":"13","author":[{"given":"Rufei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingxian","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7340-7505","authenticated-orcid":false,"given":"Tao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7835-4309","authenticated-orcid":false,"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"},{"name":"Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Jinan University, Guangzhou 510632, China"},{"name":"Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"\u00c1vila, C., Vinay, J.I., Arese, M., Saso, L., and Rodrigo, R. 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