{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:40:00Z","timestamp":1791153600260,"version":"4.1.0"},"reference-count":84,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1,5]]},"abstract":"<jats:p>Amyloid-\u03b2 peptide (A\u03b2) accumulation in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration. We have recently demonstrated that A\u03b2 induced oligodendrocyte (OLG) apoptosis, suggesting a role in white matter pathology in AD. Here, we explore the molecular mechanisms involved in A\u03b2-induced OLG death, examining the potential role of ceramide, a known apoptogenic mediator. Both A\u03b2 and ceramide induced OLG death. In addition, A\u03b2 activated neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase, resulting in increased ceramide generation. Blocking ceramide degradation with N-oleoyl-ethanolamine exacerbated A\u03b2 cytotoxicity; and addition of bacterial sphingomyelinase (mimicking cellular nSMase activity) induced OLG death. Furthermore, nSMase inhibition by 3-O-methyl-sphingomyelin or by gene knockdown using antisense oligonucleotides attenuated A\u03b2-induced OLG death. Glutathione (GSH) precursors inhibited A\u03b2 activation of nSMase and prevented OLG death, whereas GSH depletors increased nSMase activity and A\u03b2-induced death. These results suggest that A\u03b2 induces OLG death by activating the nSMase\u2013ceramide cascade via an oxidative mechanism.<\/jats:p>","DOI":"10.1083\/jcb.200307017","type":"journal-article","created":{"date-parts":[[2004,1,6]],"date-time":"2004-01-06T04:03:08Z","timestamp":1073361788000},"page":"123-131","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":257,"title":["Amyloid-\u03b2 peptide induces oligodendrocyte death by activating the neutral sphingomyelinase\u2013ceramide pathway"],"prefix":"10.1083","volume":"164","author":[{"given":"Jiunn-Tay","family":"Lee","sequence":"first","affiliation":[{"name":"3Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Xu","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Moo","family":"Lee","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Ku","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"2Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-I","family":"Yang","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawei","family":"Chen","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Y.","family":"Hsu","sequence":"additional","affiliation":[{"name":"1Center for the Study of Nervous System Injury, Department of Neurology"},{"name":"4Taipei Medical University, Taipei 110, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,1,5]]},"reference":[{"key":"2023072214493407600_BIB1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1126\/science.2118682","volume":"249","year":"1990","journal-title":"Science."},{"key":"2023072214493407600_BIB2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0024-3205(86)90083-4","volume":"38","year":"1986","journal-title":"Life Sci."},{"key":"2023072214493407600_BIB3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1073\/pnas.80.3.707","volume":"80","year":"1983","journal-title":"Proc. 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