title: Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response.
abstract: 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.
authors.affiliation: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA. gxp7@po.cwru.edu
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Marta A
authors.initials: MA
authors.lastname: Taddeo
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Tania
authors.initials: T
authors.lastname: Zenteno-Savin
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Drew
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Rudolph J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010828:Physiology, Comparative