Role of mammalian target of rapamycin in hypoxic or ischemic brain injury: potential neuroprotection and limitations

Rev Neurosci. 2012 Apr 18;23(3):279-87. doi: 10.1515/revneuro-2012-0001.

Abstract

Hypoxic or ischemic stress causes serious brain injury via various pathologic mechanisms including suppressed protein synthesis, neuronal apoptosis, and the release of neurotoxic substances. Many neuroprotective treatments of hypoxic or ischemic brain injury rely on these pathologic mechanisms. The mammalian target of rapamycin (mTOR), an atypical Ser/Thr protein kinase, could be a novel therapeutic target. mTOR plays a critical role in regulating many activities such as protein synthesis, cell growth, and cell death. Furthermore, mTOR could promote angiogenesis, neuronal regeneration, and synaptic plasticity, reduce neuronal apoptosis, and remove neurotoxic substances, which are all closely associated with the repair and survival mechanisms of hypoxic or ischemic brain injury. Although there is currently controversy with regard to regulating the activation of mTOR, the effective neuroprotective functions resulting from mTOR activation have been confirmed by various studies. Considering the potential capability for mTOR in regulating the repair and survival mechanisms of hypoxic or ischemic brain injury, mTOR may be a novel target for neuroprotective treatment.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Biotransformation / drug effects
  • Biotransformation / physiology
  • Humans
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Neovascularization, Physiologic / physiology
  • Nerve Regeneration / physiology
  • Nerve Tissue Proteins / biosynthesis
  • Neuronal Plasticity
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / metabolism
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Neurotoxins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases