Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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

Author(s): 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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Article Details

VOLUME: 7
ISSUE: 4
Year: 2007
Page: [251 - 258]
Pages: 8
DOI: 10.2174/187152407783220805
Price: $58