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

Hui Cheng, James Woodgett, Mia Maamari, Thomas Force

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations


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".

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Issue number4
StatePublished - Oct 2011
Externally publishedYes


  • Cardiac hypertrophy
  • Glycogen synthase kinase 3
  • Metabolism
  • Therapeutic potential

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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