Does cyclic dependent kinase 5 play a significant role in determination of stroke outcome? Possible therapeutic implications

Slevin, Mark, Grau-Olivares, Marta, Gaffney, John, Kumar, Patricia, Hussain, Sajjad, Kumar, Shant and Krupinski, Jerzy (2007) Does cyclic dependent kinase 5 play a significant role in determination of stroke outcome? Possible therapeutic implications. Central nervous system agents in medicinal chemistry, 7 (4). pp. 251-258. ISSN 1871-5249

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Abstract

Ischaemic stroke is a leading cause of death and disability in the Western world and usually occurs as a consequence of progressing atherothrombosis resulting in embolism and associated local tissue damage due to loss of cell membrane integrity and altered signal transduction activity. Survival of neurones, particularly in peri-infarcted regions determines the extent of patient recovery. A significant proportion of neurones in these areas undergo programmed cell death by apoptosis, resulting in a worse prognosis. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion, enhanced neuronal survival and improved recovery. Recent evidence has suggested that both angiogenesis and neuronal survival may be affected following activation of cyclin-dependent kinase-5 (Cdk5). In this review, the functional roles of Cdk5 in stroke will be described, followed by an analysis and comparison of available pharmacological inhibitors with a view to their potential use in the future treatment of this disease.