NDLI: Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shabanzadeh, A. P. D'Onofrio, P. M. Monnier, P. P. Koeberle, P. D.
Description	Country affiliation: Canada Author Affiliation: Shabanzadeh AP ( Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Canada.); D'Onofrio PM ( Toronto Western Research Institute, Toronto Western Hospital, Toronto, Canada.); Monnier PP ( Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Canada.); Koeberle PD ( Graduate Department of Rehabilitation Science, University of Toronto, Toronto, Canada.)
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.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2015.272
Journal	Cell Death and Disease
Volume Number	6
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-11-05
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Neuroprotective Agents Research Support, Non-u.s. Gov't Stroke Caspase 8 Neurons Reperfusion Injury Drug Therapy Rats, Sprague-dawley Retina Pharmacology Metabolism Molecular Targeted Therapy Caspase Inhibitors Drug Effects Discipline Cell Biology Pathology Animals Enzymology Caspase 6 Apoptosis
Content Type	Text
Resource Type	Article

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