Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?

Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative... The etiology of nerve cell death in neuronal degenerative diseases is unknown, but it has been hypothesized that excitotoxic mechanisms may play a role. Such mechanisms may play a role in diseases such as Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. In these illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden release of glutamate, such as occurs in ischemia. One possibility, however, is that a defect in mitochondrial energy metabolism could secondarily lead to slow excitotoxic neuronal death, by making neurons more vulnerable to endogenous glutamate. With reduced oxidative metabolism and partial cell membrane depolarization, voltage‐dependent N‐methyl‐D‐apartate (NMDA) receptor ion channels would be more easily activated. In addition, several other processes involved in buffering intracellular calcium may be impaired. Recent studies in experimental animals showed that mitochondrial toxins can result in a pattern of neuronal degeneration closely resembling that seen in Huntington's disease, which can be blocked with NMDA antagonists. NMDA antagonists also block neuronal degeneration induced by 1‐methyl‐4‐phenylpyridium, which has been implicated in experimental models of Parkinson's disease. The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging. If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?

Annals of Neurology, Volume 31 (2) – Feb 1, 1992

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Publisher
Wiley
Copyright
Copyright © 1992 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
D.O.I.
10.1002/ana.410310202
Publisher site
See Article on Publisher Site

Abstract

The etiology of nerve cell death in neuronal degenerative diseases is unknown, but it has been hypothesized that excitotoxic mechanisms may play a role. Such mechanisms may play a role in diseases such as Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. In these illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden release of glutamate, such as occurs in ischemia. One possibility, however, is that a defect in mitochondrial energy metabolism could secondarily lead to slow excitotoxic neuronal death, by making neurons more vulnerable to endogenous glutamate. With reduced oxidative metabolism and partial cell membrane depolarization, voltage‐dependent N‐methyl‐D‐apartate (NMDA) receptor ion channels would be more easily activated. In addition, several other processes involved in buffering intracellular calcium may be impaired. Recent studies in experimental animals showed that mitochondrial toxins can result in a pattern of neuronal degeneration closely resembling that seen in Huntington's disease, which can be blocked with NMDA antagonists. NMDA antagonists also block neuronal degeneration induced by 1‐methyl‐4‐phenylpyridium, which has been implicated in experimental models of Parkinson's disease. The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging. If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects.

Journal

Annals of NeurologyWiley

Published: Feb 1, 1992

References

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