Activating Akt and the brain's resources to drive cellular survival and prevent inflammatory injury

Histol Histopathol. 2005 Jan;20(1):299-315. doi: 10.14670/HH-20.299.

Abstract

Protein kinase B, also known as Akt, is a serine/threonine kinase and plays a critical role in the modulation of cell development, growth, and survival. Interestingly, Akt is ubiquitously expressed throughout the body, but its expression in the nervous system is substantially up-regulated during cellular stress, suggesting a more expansive role for Akt in the nervous system that may involve cellular protection. In this regard, a body of recent work has identified a robust capacity for Akt and its downstream substrates to foster both neuronal and vascular survival during apoptotic injury. Cell survival by Akt is driven by the modulation of both intrinsic cellular pathways that oversee genomic DNA integrity and extrinsic mechanisms that control inflammatory microglial activation. A series of distinct pathways are regulated by Akt that include the Forkhead family of transcription factors, GSK-3 beta, beta-catenin, c-Jun, CREB, Bad, IKK, and p53. Culminating below these substrates of Akt are the control of caspase mediated pathways that promote genomic integrity as well as prevent inflammatory cell demise. With further levels of progress in defining the cellular role of Akt, the attractiveness of Akt as a vital and broad cytoprotectant for both neuronal and vascular cell populations should continue to escalate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Brain / drug effects*
  • Carrier Proteins / metabolism
  • Cell Survival / drug effects
  • Forkhead Transcription Factors
  • Humans
  • Inflammation / drug therapy*
  • Nuclear Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / drug effects*
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / drug effects*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Transcription Factors / metabolism
  • bcl-Associated Death Protein

Substances

  • BAD protein, human
  • Carrier Proteins
  • Forkhead Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • bcl-Associated Death Protein
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt