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Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.

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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Ivins KJ,Thornton PL,Rohn TT,Cotman CW

doi

10.1006/nbdi.1999.0268

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

440-9

issue

5

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(99)90268-1

journal_volume

6

pub_type

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