CaMKII in cerebral ischemia

Steven J. Coultrap, Rebekah S. Vest, Nicole M. Ashpole, Andy Hudmon, K. Ulrich Bayer

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Ischemic insults on neurons trigger excessive, pathological glutamate release that causes Ca 2+ overload resulting in neuronal cell death (excitotoxicity). The Ca 2+ /calmodulin (CaM)-dependent protein kinase II (CaMKII) is a major mediator of physiological excitatory glutamate signals underlying neuronal plasticity and learning. Glutamate stimuli trigger autophosphorylation of CaMKII at T286, a process that makes the kinase autonomous (partially active independent from Ca 2+ stimulation) and that is required for forms of synaptic plasticity. Recent studies suggested autonomous CaMKII activity also as potential drug target for post-insult neuroprotection, both after glutamate insults in neuronal cultures and after focal cerebral ischemia in vivo. However, CaMKII and other members of the CaM kinase family have been implicated in regulation of both neuronal death and survival. Here, we discuss past findings and possible mechanisms of CaM kinase functions in excitotoxicity and cerebral ischemia, with a focus on CaMKII and its regulation.

Original languageEnglish
Pages (from-to)861-872
Number of pages12
JournalActa Pharmacologica Sinica
Volume32
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Brain Ischemia
Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinases
Glutamic Acid
Neuronal Plasticity
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cell Death
Phosphotransferases
Learning
Neurons
Pharmaceutical Preparations

Keywords

  • brain ischemia
  • CaM kinases
  • CaMKII
  • excitotoxicity
  • glutamate
  • stroke

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Coultrap, S. J., Vest, R. S., Ashpole, N. M., Hudmon, A., & Bayer, K. U. (2011). CaMKII in cerebral ischemia. Acta Pharmacologica Sinica, 32(7), 861-872. https://doi.org/10.1038/aps.2011.68

CaMKII in cerebral ischemia. / Coultrap, Steven J.; Vest, Rebekah S.; Ashpole, Nicole M.; Hudmon, Andy; Bayer, K. Ulrich.

In: Acta Pharmacologica Sinica, Vol. 32, No. 7, 07.2011, p. 861-872.

Research output: Contribution to journalArticle

Coultrap, SJ, Vest, RS, Ashpole, NM, Hudmon, A & Bayer, KU 2011, 'CaMKII in cerebral ischemia', Acta Pharmacologica Sinica, vol. 32, no. 7, pp. 861-872. https://doi.org/10.1038/aps.2011.68
Coultrap SJ, Vest RS, Ashpole NM, Hudmon A, Bayer KU. CaMKII in cerebral ischemia. Acta Pharmacologica Sinica. 2011 Jul;32(7):861-872. https://doi.org/10.1038/aps.2011.68
Coultrap, Steven J. ; Vest, Rebekah S. ; Ashpole, Nicole M. ; Hudmon, Andy ; Bayer, K. Ulrich. / CaMKII in cerebral ischemia. In: Acta Pharmacologica Sinica. 2011 ; Vol. 32, No. 7. pp. 861-872.
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