Abstract
The development of small molecule kinase inhibitors as potential cancer therapeutics is an area of intense interest, and a subset of these agents target cyclindependent kinase (CDK) activity. Ten distinct CDKs (1-9, 11), when paired with their cyclin activators, are integral to such diverse processes as cell cycle control, neuronal development, and transcriptional regulation. Mutation and / or aberrant expression of certain CDKs and their regulatory counterparts are associated with uncontrolled proliferation and tumorigenesis. As such, CDK selective inhibitors (CDKIs) that attenuate or prevent tumor growth have been developed. Recently, interest in the therapeutic potential of CDKIs has expanded to include neurodegenerative diseases, where dysregulated CDK activity has been linked to the pathogenesis of Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), and stroke. Specifically, aberrant activation of cell cycle CDKs or CDK5 is associated with apoptosis and neuronal dysfunction in response to various neuronal stressors. To date, CDKIs have shown promise as neuroprotective agents in the research laboratory and, in the future, may prove useful in the neurology clinic.
Keywords: cyclin-dependent kinase inhibitors, cell cycle, cancer, neurodegeneration, alzheimers disease, amyotrophic lateral sclerosis, stroke
Current Medicinal Chemistry
Title: Cyclin-Dependent Kinase Inhibitors: Cancer Killers to Neuronal Guardians
Volume: 10 Issue: 5
Author(s): E. A. Monaco III and M. L. Vallano
Affiliation:
Keywords: cyclin-dependent kinase inhibitors, cell cycle, cancer, neurodegeneration, alzheimers disease, amyotrophic lateral sclerosis, stroke
Abstract: The development of small molecule kinase inhibitors as potential cancer therapeutics is an area of intense interest, and a subset of these agents target cyclindependent kinase (CDK) activity. Ten distinct CDKs (1-9, 11), when paired with their cyclin activators, are integral to such diverse processes as cell cycle control, neuronal development, and transcriptional regulation. Mutation and / or aberrant expression of certain CDKs and their regulatory counterparts are associated with uncontrolled proliferation and tumorigenesis. As such, CDK selective inhibitors (CDKIs) that attenuate or prevent tumor growth have been developed. Recently, interest in the therapeutic potential of CDKIs has expanded to include neurodegenerative diseases, where dysregulated CDK activity has been linked to the pathogenesis of Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), and stroke. Specifically, aberrant activation of cell cycle CDKs or CDK5 is associated with apoptosis and neuronal dysfunction in response to various neuronal stressors. To date, CDKIs have shown promise as neuroprotective agents in the research laboratory and, in the future, may prove useful in the neurology clinic.
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Cite this article as:
Monaco III A. E. and Vallano L. M., Cyclin-Dependent Kinase Inhibitors: Cancer Killers to Neuronal Guardians, Current Medicinal Chemistry 2003; 10 (5) . https://dx.doi.org/10.2174/0929867033368277
DOI https://dx.doi.org/10.2174/0929867033368277 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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