Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: Beyond damage and response

George Perry*, Marta A. Taddeo, Akihiko Nunomura, Xiongwei Zhu, Tania Zenteno-Savin, Kelly L. Drew, Shun Shimohama, Jesús Avila, Rudolph J. Castellani, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


In this review, we consider comparative aspects of the biology and pathology of oxygen radicals in neurodegenerative disease and how these findings have influenced our concept of oxidative stress. The common definition of oxidative stress is a breach of antioxidant defenses by oxygen radicals leading to damage to critical molecules and disrupted physiology. Inherent in this definition is that oxidative stress is an unstable situation, for if there is net damage, viability of the system decreases with time, leading to disequilibria and death. While this circumstance defines acute conditions, such as stroke and head trauma which result in dysfunction and death, it does not fit physiological situations or chronic diseases closely aligned to normal physiology. Therefore, we propose that oxidative modifications in Alzheimer disease may actually serve as a homeostatic response to stress resulting in a shift of neuronal priority from normal function to basic survival. This phenomenon is comparable to normal physiological conditions of metabolic decrease, such as those seen in hibernation and estivation. Thus, Alzheimer disease could be seen as part of normal aging that includes additional pathology due to inadequate homeostatic response.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalComparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Issue number4
StatePublished - Dec 1 2002
Externally publishedYes


  • Aging
  • Alzheimer disease
  • Hibernation
  • Homeostasis
  • Iron
  • Mitochondria
  • Neurodegenerative disease
  • Oxidative damage
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis


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