Publication: Caspase inhibition, a potential therapeutic strategy in neurological diseases
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Date
2001
Authors
Rideout, H.J. ; Stefanis, L.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Caspases are intracellular proteases that
participate in apoptotic pathways in mammalian cells,
including neurons. Here we review evidence that caspase
inhibition, through pharmacological or molecular means,
rnay inhibit neuronal cell death in a number of in vitro
and in vivo models of neurological disease. It has
recently become clear that, at least in most cell culture
models, caspase inhibition offers only transient
protection, and that a caspase-independent death
eventually occurs. This rnay be due to irreversible
caspase-independent alterations at the leve1 of the
mitochondria. Despite concerns that targeting caspases
alone rnay prove insufficient to truly reverse the effects
of various death stimuli, in vivo studies indicate that
caspase inhibition promotes survival and functional
outcome in a variety of neurological disease models. In
addition, studies of human post-mortem material suggest
that caspases are activated in certain human neurological
diseases. Caspase inhibition rnay therefore provide a
novel strategy for the treatment of such disorders.
Caspas'es, through the generation of toxic fragments of
critica1 protein substrates, rnay also be involved in
earlier steps of neuronal dysfunction, such as protein
aggregation in Huntington's and Alzheimer's disease,
and therefore caspase inhibition rnay be of additional
value in the treatment of these particular disorders.
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