Author(s): Ivins KJ, Thornton PL, Rohn TT, Cotman CW
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Abstract The Alzheimer disease-associated beta-amyloid peptide has been shown to induce apoptotic neuronal death. In the present study, we test the hypothesis that the apoptotic pathway activated by beta-amyloid is similar to the pathway activated by the Fas/TNFR family of death receptors, which requires caspase-8 activity and adaptor proteins such as FADD. We demonstrate that the selective caspase-8 inhibitor IETD-fmk blocks neuronal death induced by beta-amyloid. Furthermore, using viral-mediated gene delivery, we show that neurons expressing dominant-negative FADD are protected from apoptosis induced by beta-amyloid. Together these results indicate that the apoptotic pathway activated by beta-amyloid requires both caspase-8 activity and FADD. These findings further support the hypothesis that beta-amyloid might initiate apoptosis by cross-linking death receptors of the Fas/TNFR family. Copyright 1999 Academic Press.
This article was published in Neurobiol Dis
and referenced in Journal of Clinical & Experimental Pathology