Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke
Identifieur interne : 000517 ( Main/Exploration ); précédent : 000516; suivant : 000518Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke
Auteurs : A P Shabanzadeh [Canada] ; P M D'Onofrio [Canada] ; P P Monnier [Canada] ; P D Koeberle [Canada]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2015.
Abstract
Previous studies show that caspase-6 and caspase-8 are involved in neuronal apoptosis and regenerative failure after trauma of the adult central nervous system (CNS). In this study, we evaluated whether caspase-6 or -8 inhibitors can reduce cerebral or retinal injury after ischemia. Cerebral infarct volume, relative to appropriate controls, was significantly reduced in groups treated with caspase-6 or -8 inhibitors. Concomitantly, these treatments also reduced neurological deficits, reduced edema, increased cell proliferation, and increased neurofilament levels in the injured cerebrum. Caspase-6 and -8 inhibitors, or siRNAs, also increased retinal ganglion cell survival at 14 days after ischemic injury. Caspase-6 or -8 inhibition also decreased caspase-3, -6, and caspase-8 cleavage when assayed by western blot and reduced caspase-3 and -6 activities in colorimetric assays. We have shown that caspase-6 or caspase-8 inhibition decreases the neuropathological consequences of cerebral or retinal infarction, thereby emphasizing their importance in ischemic neuronal degeneration. As such, caspase-6 and -8 are potential targets for future therapies aimed at attenuating the devastating functional losses that result from retinal or cerebral stroke.
Url:
DOI: 10.1038/cddis.2015.272
PubMed: 26539914
PubMed Central: 4670918
Affiliations:
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