{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:59:05Z","timestamp":1779364745578,"version":"3.53.0"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AT10980"],"award-info":[{"award-number":["AT10980"]}]},{"name":"NIH","award":["AG069229"],"award-info":[{"award-number":["AG069229"]}]},{"name":"NIH","award":["1IK6 BX004982"],"award-info":[{"award-number":["1IK6 BX004982"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["AT10980"],"award-info":[{"award-number":["AT10980"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["AG069229"],"award-info":[{"award-number":["AG069229"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1IK6 BX004982"],"award-info":[{"award-number":["1IK6 BX004982"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Tay-Sachs disease (TSD) is a progressive heritable neurodegenerative disorder characterized by the deficiency of the lysosomal \u03b2-hexosaminidase enzyme (Hex\u2212\/\u2212) and the storage of GM2 ganglioside, as well as other related glycoconjugates. Along with motor difficulties, TSD patients also manifest a gradual loss of skills and behavioral problems, followed by early death. Unfortunately, there is no cure for TSD; however, research on treatments and therapeutic approaches is ongoing. This study underlines the importance of gemfibrozil (GFB), an FDA-approved lipid-lowering drug, in inhibiting the disease process in a transgenic mouse model of Tay-Sachs. Oral administration of GFB significantly suppressed glial activation and inflammation, while also reducing the accumulation of GM2 gangliosides\/glycoconjugates in the motor cortex of Tay-Sachs mice. Furthermore, oral GFB improved behavioral performance and increased the life expectancy of Tay-Sachs mice. While investigating the mechanism, we found that oral administration of GFB increased the level of peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) in the brain of Tay-Sachs mice, and that GFB remained unable to reduce glycoconjugates and improve behavior and survival in Tay-Sachs mice lacking PPAR\u03b1. Our results indicate a beneficial function of GFB that employs a PPAR\u03b1-dependent mechanism to halt the progression of TSD and increase longevity in Tay-Sachs mice.<\/jats:p>","DOI":"10.3390\/cells12242791","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T03:03:33Z","timestamp":1702004613000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lipid-Lowering Drug Gemfibrozil Protects Mice from Tay-Sachs Disease via Peroxisome Proliferator-Activated Receptor \u03b1"],"prefix":"10.3390","volume":"12","author":[{"given":"Sumita","family":"Raha","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-3581","authenticated-orcid":false,"given":"Debashis","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Paidi","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-9598","authenticated-orcid":false,"given":"Kalipada","family":"Pahan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"},{"name":"Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2174\/1566523218666180404162622","article-title":"Genetics and Therapies for GM2 Gangliosidosis","volume":"18","author":"Zaccariotto","year":"2018","journal-title":"Curr. 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