The mitochondrial permeability transition as a target for neuroprotection.
Mitochondria serve as checkpoints and amplifiers on cell death pathways. In the central nervous system, mitochondrial involvement seems essential for normal expression of cell death phenotypes, and interference with these pathways thus seems a reasonable approach to neuroprotection. We have been involved in examining the potential involvement of the mitochondrial permeability transition (mPT) as one of several possible mechanisms by which mitochondria may be drawn into these death cascades. This possibility, though still controversial, is supported by evidence that factors that may stimulate mPT induction are associated with some forms of cell death (e.g., in stroke) and are modulated by diseases of the central nervous system (e.g., Huntington's). Evidence of neuroprotection seen with compounds such as N -Met-Val cyclosporine also support this possibility.
Kristal
Bruce S
BS
Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Ave., White Plains, New York 10605, USA. bkristal@burke.org
Stavrovskaya
Irina G
IG
Narayanan
Malini V
MV
Krasnikov
Boris F
BF
Brown
Abraham M
AM
Beal
M Flint
MF
Friedlander
Robert M
RM
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000378:metabolism
D000447:Aldehydes; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D015032:Zinc; D002118:Calcium