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Insulin disregulation and neurodegeneration: a possible role for CDK5
Author(s) -
Khost Daniel Emerson,
Cotton Renita,
Aguanno Ann
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.593.1
Subject(s) - cyclin dependent kinase 5 , neurodegeneration , biology , neuroscience , microbiology and biotechnology , cyclin dependent kinase , kinase , cell cycle , cancer research , immunology , disease , cell , cyclin dependent kinase 2 , protein kinase a , medicine , genetics
Cyclin dependent kinase 5 (CDK5) is a member of the cyclin dependent kinase family that, unlike its fellow CDKs, is not involved in regulation of the cell cycle, but is instead predominantly active in terminally differentiated neurons. CDK5's role in the developing nervous system in regards to dendrite extension, synapse formation, axonal guidance, as well as an array of other functions has been well studied over the years. It has also been implicated in Alzheimer's Disease (AD), where disregulation of CDK5 via the cleavage of its activating partner p35 to p25 contributes to the formation of neurofibrillary tangles. CDK5 activity is also found in other tissues, including the pancreas, where it is believed to play a role in insulin exocytosis. A correlation between Type II diabetes and AD has led to the hypothesis that a connection exists between insulin disregulation and neurodegeneration, and as CDK5 is active in both tissues it represents a possible common feature in the two pathologies. To study this, our lab models the developing and mature nervous and endocrine system using PC12 and AR42J cell lines, respectively. We induce transdifferentiation of both of these cells lines with various growth factors and investigate the impact of CDK5's chemical inhibition. Our results suggest a role for CDK5 in the link between insulin disregulation and neurodegenerative disease. Funding from the US Dept. of Education and the Rose M Badgely Charitable Trust