Aging, energy, and oxidative stress in neurodegenerative diseases

Aging, energy, and oxidative stress in neurodegenerative diseases The etiology of neurodegenerative diseases remains enigmatic; however, evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage is increasingly compelling. It is likely that there is a complex interplay between these mechanisms. A defect in energy metabolism may lead to neuronal depolarization, activation of N‐methyl‐D‐aspartate excitatory amino acid‐receptors, and increases in intracellular calcium, which are buffered by mitochondria. Mitochondria are the major intracellular source of free radicals, and increased mitochondrial calcium concentrations enhance free radical generation. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age‐dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors. All of these approaches appear promising in experimental studies and are now being applied to human studies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Aging, energy, and oxidative stress in neurodegenerative diseases

Annals of Neurology, Volume 38 (3) – Sep 1, 1995

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Publisher
Wiley
Copyright
Copyright © 1995 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
D.O.I.
10.1002/ana.410380304
Publisher site
See Article on Publisher Site

Abstract

The etiology of neurodegenerative diseases remains enigmatic; however, evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage is increasingly compelling. It is likely that there is a complex interplay between these mechanisms. A defect in energy metabolism may lead to neuronal depolarization, activation of N‐methyl‐D‐aspartate excitatory amino acid‐receptors, and increases in intracellular calcium, which are buffered by mitochondria. Mitochondria are the major intracellular source of free radicals, and increased mitochondrial calcium concentrations enhance free radical generation. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age‐dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors. All of these approaches appear promising in experimental studies and are now being applied to human studies.

Journal

Annals of NeurologyWiley

Published: Sep 1, 1995

References

  • Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?
    Beal, Beal
  • Generation of H 2 O 2 in brain mitochondria
    Patole, Patole; Swaroop, Swaroop; Ramasarma, Ramasarma
  • Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain
    Mecocci, Mecocci; MacGarvey, MacGarvey; Kaufman, Kaufman
  • Rapid ATP loss caused by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine in mouse brain
    Chan, Chan; DeLanney, DeLanney; Irwin, Irwin
  • 1‐Methyl‐4‐phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism
    Storey, Storey; Hyman, Hyman; Jenkins, Jenkins
  • Anatomic and disease specificity of NADH CoQ 1 reductase (complex I) deficiency in Parkinson's disease
    Schapira, Schapira; Mann, Mann; Cooper, Cooper
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    Hattori, Hattori; Tanaka, Tanaka; Ozawa, Ozawa
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    Mecocci, Mecocci; MacGarvey, MacGarvey; Beal, Beal
  • Coenzyme Q 10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate
    Beal, Beal; Henshaw, Henshaw; Jenkins, Jenkins

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