{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:19:53Z","timestamp":1791011993512,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T00:00:00Z","timestamp":1097452800000},"content-version":"vor","delay-in-days":3632,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[1994,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The direct neurotoxic action of the \u03b2\u2010amyloid protein, the major constituent of senile plaques, may represent the underlying cause of neuronal degeneration observed in Alzheimer's disease. The apoptotic\u2010mediated neuronal death induced by \u03b2\u2010amyloid appears to reside in its ability to form Ca<jats:sup>&gt;2+<\/jats:sup>\u2010permeable pores in neuronal membranes resulting in an excessive influx of Ca<jats:sup>2+<\/jats:sup> and the induction of neurotoxic cascades. It is possible that during \u03b2\u2010amyloid exposure a Ca<jats:sup>2+<\/jats:sup>\u2010mediated increase in free radical generation may exceed the defensive capacity of cells and thus lead to cell death. Consequently, in the present study we have investigated the effect of a panoply of antioxidants and inhibitors of free radical formation on the development of \u03b2\u2010amyloid neurotoxicity. Acute exposure of rat hippocampal neurons to \u201caged\u201d \u03b2\u2010amyloid<jats:sub>25\u201335<\/jats:sub> peptide (5\u201350 m\u0308M) induced a slow, concentration\u2010dependent apoptotic neurotoxicity (25\u201385%) during a 6 day exposure. Co\u2010incubation of cultures with \u03b2\u2010amyloid<jats:sub>25\u201335<\/jats:sub> peptide (25 \u03bcM) and inhibitors of nitric oxide synthase and\/or xanthine oxidase (N<jats:sup>G<\/jats:sup>\u2010monomethyl\u2010L\u2010arginine [1 mM], N\u03c9\u2010nitro\u2010L\u2010arginine [1 mM], oxypurinol [100 m\u0308M], allopurinol [100 m\u0308M]), important mediators of nitric oxide, superoxide, and hydroxyl radical formation, did not attenuate \u03b2\u2010amyloid neurotoxicity. Similarly, a reduction in free radical generation by selective inhibition of phospholipase\u2010A<jats:sub>2<\/jats:sub> cyclooxygenase, and lipoxygenase activities with quinacrine (0.5 m\u0308M), indomethacin (50 m\u0308M), and <jats:italic>nor<\/jats:italic>\u2010dihydroguaiaretic acid (0.5 m\u0308M), respectively, did not reduce the proclivity of \u03b2\u2010amyloid to induce cell death. Exposure of cultures to catalase (25 U\/ml) and\/or superoxide dismutase (10 U\/ml) as well as the free radical scavengers vitamin E (100 m\u0308M), vitamin C (100 m\u0308M), glutathione (100 m\u0308M), L\u2010cysteine (100 m\u0308M), N\u2010acetyl\u2010cysteine (100 m\u0308M), deferoxamine (5 m\u0308M), or haemoglobin (35 m\u0308g\/ml) failed to attenuate the neurotoxic action of \u03b2\u2010amyloid. On the other hand, pre\u2010treatment of cultures with subtoxic concentrations of \u03b2\u2010amyloid peptide significantly increased the vulnerability of neurons to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure and suggest that \u03b2\u2010amyloid peptide renders neurons more sensitive to free radical attack. However, a potential \u03b2\u2010amyloid\u2010mediated increase in free radical formation is not a proximate cause of the neurotoxic mechanism of \u03b2\u2010amyloid in vitro. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.490390416","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T02:03:19Z","timestamp":1104544999000},"page":"494-505","source":"Crossref","is-referenced-by-count":76,"title":["Inhibitors of free radical formation fail to attenuate direct \u03b2\u2010amyloid<sub>25\u201335<\/sub> peptide\u2010mediated neurotoxicity in rat hippocampal cultures"],"prefix":"10.1002","volume":"39","author":[{"given":"B. P.","family":"Lockhart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Benicourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010L.","family":"Junien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Privat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,11]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.567"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90837-B"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2571"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb13658.x"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1508"},{"key":"e_1_2_1_7_1","first-page":"1439","article-title":"Nimodipine\u2010sensitive, \u03b2\u2010amyloid (25\u201035)\u2010induced [Ca2+]i responses in single cultured rat hippocampal neurons","volume":"18","author":"Chisholm JC","year":"1992","journal-title":"Soc Neurosci Abstr"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199112000-00008"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90060-B"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90805-U"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7901908"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6368"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90145-D"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490290116"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1987.tb10014.x"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/362543a0"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199305000-00015"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","unstructured":"FraserPE L\u00e9vesqueL McLachlanDR(1994): Alzheimer A\u03b2 amyloid forms an inhibitory neuronal substrate.J Neurochem1227\u20131230.","DOI":"10.1046\/j.1471-4159.1994.62031227.x"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/357500a0"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/359322a0"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2190001"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3270"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80066-N"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199306000-00041"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3287616"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235659"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91355-K"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7247"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/364535a0"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.7951"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/368756a0"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03275.x"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-02-00376.1992"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(93)90009-B"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90295-X"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb07480.x"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.003431"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1989.tb22646.x"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-04-01441.1993"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(93)90070-3"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90331-9"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91553-D"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(91)90014-9"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199209000-00012"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-04-01676.1993"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.3.671"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90326-G"},{"key":"e_1_2_1_48_1","first-page":"288","article-title":"Nordihydroguaiaretic acid (NDGA) attenuates slow excitatory amino acid\u2010induced neuronal degeneration in cortical cultures","volume":"16","author":"Rose K","year":"1990","journal-title":"Soc Neurosci Abstr"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2628"},{"key":"e_1_2_1_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb10972.x"},{"key":"e_1_2_1_51_1","first-page":"1447","article-title":"Beta\u2010amyloid protein potentiates H2O2\u2010induced neuron degeneration in vitro","volume":"17","author":"Saunders RD","year":"1991","journal-title":"Soc Neurosci Abstr"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(84)90070-9"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.4.1470"},{"key":"e_1_2_1_55_1","first-page":"373","article-title":"Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro","volume":"45","author":"Simmons LK","year":"1994","journal-title":"Mol Pharmacol"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90519-Q"},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7789"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91691-7"},{"key":"e_1_2_1_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1972.tb27851.x"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2474201"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2218531"},{"key":"e_1_2_1_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1988.tb14105.x"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62010372.x"},{"key":"e_1_2_1_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4533"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.490390416","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.490390416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T08:24:06Z","timestamp":1698222246000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.490390416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,11]]}},"alternative-id":["10.1002\/jnr.490390416"],"URL":"https:\/\/doi.org\/10.1002\/jnr.490390416","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11]]}}}