Does Cyclic Dependent Kinase 5 Play a Significant Role in Determination of Stroke Outcome? Possible Therapeutic Implications

Mark      Slevin; Marta      Grau-Olivares; John      Gaffney; Pat      Kumar; Sajjad      Hussain; Shant      Kumar; Jurek      Krupinski

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 cyclindependent 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.

Keywords: Cdk5, stroke, hypoxia-reperfusion, neurones, angiogenesis, pharmacological inhibition, apoptosis

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