{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:36:27Z","timestamp":1777545387982,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG050431"],"award-info":[{"award-number":["AG050431"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the <jats:italic>Cln2<\/jats:italic> gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid\u2010protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL. Therefore, we administered gemfibrozil (gem), an food and drug administration (FDA)\u2010approved lipid\u2010lowering drug, which has been shown to stimulate lysosomal biogenesis and induce anti\u2010inflammation, orally, at a dose of 7.5\u00a0mg\/kg body wt\/day to <jats:italic>Cln2<\/jats:italic><jats:sup>(\u2212\/\u2212)<\/jats:sup> mice. We observed that gem\u2010fed <jats:italic>Cln2<\/jats:italic><jats:sup>(\u2212\/\u2212)<\/jats:sup> mice lived longer by more than 10\u00a0weeks and had better motor activity compared to vehicle (0.1% Methyl cellulose) treatment. Gem treatment lowered the burden of storage materials, increased anti\u2010inflammatory factors like SOCS3 and IL\u20101Ra, up\u2010regulated anti\u2010apoptotic molecule like phospho\u2010Bad, and reduced neuronal apoptosis in the brain of <jats:italic>Cln2<\/jats:italic><jats:sup>(\u2212\/\u2212)<\/jats:sup> mice. Collectively, this study reinforces a neuroprotective role of gem that may be of therapeutic interest in improving the quality of life in LINCL patients.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13987-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13987","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T13:42:43Z","timestamp":1487166163000},"page":"423-435","source":"Crossref","is-referenced-by-count":33,"title":["Gemfibrozil, food and drug administration\u2010approved lipid\u2010lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis"],"prefix":"10.1111","volume":"141","author":[{"given":"Arunava","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh Babu","family":"Rangasamy","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushbu K.","family":"Modi","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Illinois 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