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J Mol Cell Cardiol. 2011 Oct;51(4):607-13. doi: 10.1016/j.yjmcc.2010.11.020. Epub 2010 Dec 13.

Targeting GSK-3 family members in the heart: a very sharp double-edged sword.

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1
Center for Translational Medicine and Cardiology Division, Thomas Jefferson University Hospital, Philadelphia, PA, USA. hui.cheng@jefferson.edu

Abstract

The GSK-3 family of serine/threonine kinases, which is comprised of two isoforms (α and β), was initially identified as a negative regulator of glycogen synthase, the rate limiting enzyme of glycogen synthesis [1,2]. In the 30 years since its initial discovery, the family has been reported to regulate a host of additional cellular processes and, consequently, disease states such as bipolar disorders, diabetes, inflammatory diseases, cancer, and neurodegenerative diseases including Alzheimer's Disease and Parkinson's Disease [3,4]. As a result, there has been intense interest on the part of the pharmaceutical industry in developing small molecule antagonists of GSK-3. Herein, we will review the roles played by GSK-3s in the heart, focusing primarily on recent studies that have employed global and tissue-specific gene deletion. We will highlight roles in various pathologic processes, including pressure overload and ischemic injury, focusing on some striking isoform-specific effects of the family. Due to space limitations and/or the relatively limited data in gene-targeted mice, we will not be addressing the family's roles in ischemic pre-conditioning or its many interactions with various pro- and anti-apoptotic factors. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

PMID:
21163265
PMCID:
PMC3075376
DOI:
10.1016/j.yjmcc.2010.11.020
[Indexed for MEDLINE]
Free PMC Article

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