{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:11:02Z","timestamp":1790993462902,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":1095,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Amyloid \u03b2 peptides (A\u03b2P) deposit as plaques in vascular and parenchymal areas of Alzheimer's disease (AD) tissues and Down's syndrome patients. Although neuronal toxicity is a feature of late stages of AD, vascular pathology appears to be a feature of all stages of AD. Globular and nonfibrillar A\u03b2Ps are continuously released during normal cellular metabolism, form calcium\u2010permeable channels, and alter cellular calcium level. We used atomic force microscopy, laser confocal microscopy, and calcium imaging to examine the real\u2010time and acute effects of fresh and globular A\u03b2P\n                    <jats:sub>1\u201342<\/jats:sub>\n                    , A\u03b2P\n                    <jats:sub>1\u201340<\/jats:sub>\n                    , and A\u03b2P\n                    <jats:sub>25\u201335<\/jats:sub>\n                    on cultured endothelial cells. A\u03b2Ps induced morphological changes that were observed within minutes after A\u03b2P treatment and led to eventual cellular degeneration. Cellular morphological changes were most sensitive to A\u03b2P\n                    <jats:sub>1\u201342<\/jats:sub>\n                    .A\u03b2P\n                    <jats:sub>1\u201342<\/jats:sub>\n                    \u2010induced morphological changes were observed at nanomolar concentrations and were accompanied by an elevated cellular calcium level. Morphological changes were prevented by anti\u2010A\u03b2P antibody, A\u03b2P\u2010channel antagonist zinc, and the removal of extracellular calcium, but not by tachykinin neuropeptide, voltage\u2010sensitive calcium channel blocker cadmium, or antioxidants DTT and Trolox. Thus, nanomolar fresh and globular A\u03b2P\n                    <jats:sub>1\u201342<\/jats:sub>\n                    induces rapid cellular degeneration by elevating intracellular calcium, most likely via calcium\u2010permeable A\u03b2P channels and not by its interaction with membrane receptors or by activating oxidative pathways. Such rapid degeneration also suggests that the plaques, and especially fibrillar A\u03b2Ps, may not have a direct causative role in AD pathogenic cascades.\u2014Bhatia, R., Lin H., Lal, R. Fresh and globular amyloid \u03b2 protein (1\u201342) induces rapid cellular degeneration: evidence for A\u03b2 P channel\u2010mediated cellular toxicity\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 14, 1233\u20131243 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.14.9.1233","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T07:59:22Z","timestamp":1516262362000},"page":"1233-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":196,"title":["Fresh and globular amyloid \u03b2 protein (1\u201342) induces rapid cellular degeneration: evidence for A\u03b2P channel\u2010mediated cellular toxicity"],"prefix":"10.1096","volume":"14","author":[{"given":"Rajinder","family":"Bhatia","sequence":"first","affiliation":[{"name":"Neuroscience Research Institute University of California  Santa Barbara California 93106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Lin","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute University of California  Santa Barbara California 93106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratneshwar","family":"Lal","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute University of California  Santa Barbara California 93106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,6]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.1081"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/359322a0"},{"key":"e_1_2_4_4_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0896-6273(95)90079-9","article-title":"Characterization of stable complexes involving apolipoprotein E and the amyloid beta peptide in Alzheimer's disease brain","volume":"15","author":"Nashlund J.","year":"1995","journal-title":"Neuron"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.370"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/383710a0"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5113"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-864"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294173"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.2092"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00006-7"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000106934"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6743"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/380168a0"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1994.tb01660.x"},{"key":"e_1_2_4_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)00180-V"},{"key":"e_1_2_4_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02816103"},{"key":"e_1_2_4_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68051870.x"},{"key":"e_1_2_4_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00383-1"},{"key":"e_1_2_4_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.1997.3859"},{"key":"e_1_2_4_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0798-827"},{"key":"e_1_2_4_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi982119e"},{"key":"e_1_2_4_23_1","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1073\/pnas.93.4.1710","article-title":"Zn2+ interaction with Alzheimer amyloid \u03b2 protein calcium channels","volume":"83","author":"Arispe N.","year":"1996","journal-title":"Proc. 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