Mitochondrial permeability transition in acute neurodegeneration

Biochimie. Feb-Mar 2002;84(2-3):241-50. doi: 10.1016/s0300-9084(02)01381-0.


Acute neurodegeneration in man is encountered during and following stroke, transient cardiac arrest, brain trauma, insulin-induced hypoglycemia and status epilepticus. All these severe clinical conditions are characterized by neuronal calcium overload, aberrant cell signaling, generation of free radicals and elevation of cellular free fatty acids, conditions that favor activation of the mitochondrial permeability transition pore (mtPTP). Cyclosporin A (CsA) and its analog N-methyl-valine-4-cyclosporin A (MeValCsA) are potent blockers of the mtPTP and protect against neuronal death following excitotoxicity and oxygen glucose deprivation. Also, CsA and MeValCsA diminish cell death following cerebral ischemia, trauma, and hypoglycemia. Here we present data that strongly imply the mtPT in acute neurodegeneration in vivo. Compounds that readily pass the blood-brain-barrier (BBB) and block the mtPT may be neuroprotective in stroke.

Publication types

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

MeSH terms

  • Acute Disease
  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology
  • Cell Membrane Permeability / drug effects
  • Cyclosporins / administration & dosage*
  • Enzyme Inhibitors / administration & dosage*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Ion Channels / metabolism*
  • Mitochondria / physiology*
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Neurodegenerative Diseases / pathology*
  • Neurons / physiology*
  • Rats


  • Cyclosporins
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Ion Channels
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore