{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:56:04Z","timestamp":1773053764115,"version":"3.50.1"},"reference-count":26,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,9,5]]},"abstract":"<jats:p>Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas\/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP\/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo.<\/jats:p>","DOI":"10.1084\/jem.20050163","type":"journal-article","created":{"date-parts":[[2005,8,30]],"date-time":"2005-08-30T00:13:17Z","timestamp":1125360797000},"page":"575-581","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease"],"prefix":"10.1084","volume":"202","author":[{"given":"Anne M.","family":"Landau","sequence":"first","affiliation":[{"name":"1Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelvin C.","family":"Luk","sequence":"additional","affiliation":[{"name":"2Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle-Lee","family":"Jones","sequence":"additional","affiliation":[{"name":"1Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosmarie","family":"Siegrist-Johnstone","sequence":"additional","affiliation":[{"name":"1Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon Kow","family":"Young","sequence":"additional","affiliation":[{"name":"1Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edouard","family":"Kouassi","sequence":"additional","affiliation":[{"name":"4Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital"},{"name":"5Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H1T 2M4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir V.","family":"Rymar","sequence":"additional","affiliation":[{"name":"2Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Dagher","sequence":"additional","affiliation":[{"name":"3McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas F.","family":"Sadikot","sequence":"additional","affiliation":[{"name":"2Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Desbarats","sequence":"additional","affiliation":[{"name":"1Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2005,8,29]]},"reference":[{"key":"2023072513243553400_BIB1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0092-8674(00)81874-7","volume":"88","year":"1997","journal-title":"Cell."},{"key":"2023072513243553400_BIB2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainresrev.2003.08.007","volume":"44","year":"2004","journal-title":"Brain Res. 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