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Caspase inhibitors protect against neuronal apoptosis induced by cerebrospinal fluid from multiple sclerosis patients.

Abstract：

:Neuronal apoptosis has recently been implicated in multiple sclerosis (MS). Apoptotic cell death of neurons is induced in cultures exposed to cerebrospinal fluid (CSF) from MS patients. Since caspases are essential in the regulation of apoptosis, direct evidence was sought linking caspases to CSF-induced neuronal death. Caspase activity was measured in cell extracts from MS CSF-treated cultured neurons by the cleavage of caspase-1 and caspase-3 substrates. Caspase-3 activity, but not caspase-1, was induced in neuronal cultures in response to MS CSF treatment. This caspase-3 activity was inhibited in vitro by Ac-YVAD-cmk and Ac-DEVD-cmk caspase inhibitors. Treatment of MS CSF-incubated neuronal cells with these caspase inhibitors completely preserved neuronal survival and largely attenuated DNA fragmentation detected in situ. These findings show that neuronal cells are rescued from MS CSF-induced death by caspase inhibitors and suggest ways to treat MS.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

Cid C,Alvarez-Cermeño JC,Regidor I,Plaza J,Salinas M,Alcázar A

doi

10.1016/s0165-5728(02)00467-8

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

119-24

issue

1-2

eissn

0165-5728

issn

1872-8421

pii

S0165572802004678

journal_volume

136

pub_type

杂志文章

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