Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Critical Review
Akt Is a Molecular Target for Signal Transduction Therapy in Brain Ischemic Insult
Kohji FukunagaTakayuki Kawano
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2003 Volume 92 Issue 4 Pages 317-327

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Abstract

Growth factors including insulin-like growth factor-1 (IGF-1) promote cell survival in ischemic brain injury. Stimulation of IGF-1 receptor coupled with tyrosine kinase activates phosphatidylinositol 3-kinase and subsequently, protein kinase B (Akt) in hippocampal neurons. Here we introduce a new approach of signal transduction therapy for brain damage occurring in ischemic insult. As has been shown for IGF-1, intracerebroventricular injection of sodium orthovanadate, a protein tyrosine phosphatase inhibitor, prior to ischemic insult blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with an increased Akt activity in the CA1 region. We discuss here potential targets for Akt relevant to such neuroprotective activity. Our findings lead to the conclusion that Akt activity is a potential target for neuroprotective drugs in brain ischemic insult and other episodes of excitotoxic neuronal apoptosis such as seizure and Huntington’s and Parkinson’s diseases.

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© The Japanese Pharmacological Society 2003
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