Abstract

In this review I report evidence that the mainstream field of oxidative damage biology has been running fast in the wrong direction for more than 50 years. Reactive oxygen species (ROS) and chronic oxidative changes in membrane lipids and proteins found in many chronic diseases are not the result of accidental damage. Instead, these changes are the result of a highly evolved, stereotyped, and protein-catalyzed "oxidative shielding" response that all eukaryotes adopt when placed in a chemically or microbially hostile environment. The machinery of oxidative shielding evolved from pathways of innate immunity designed to protect the cell from attack and limit the spread of infection. Both oxidative and reductive stress trigger oxidative shielding. In the cases in which it has been studied explicitly, functional and metabolic defects occur in the cell before the increase in ROS and oxidative changes. ROS are the response to disease, not the cause. Therefore, it is not the oxidative changes that should be targeted for therapy, but rather the metabolic conditions that create them. This fresh perspective is relevant to diseases that range from autism, type 1 diabetes, type 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer disease. Research efforts need to be redirected. Oxidative shielding is protective and is a misguided target for therapy. Identification of the causal chemistry and environmental factors that trigger innate immunity and metabolic memory that initiate and sustain oxidative shielding is paramount for human health.

Links

Publisher Full Text

Authors

Naviaux RK

Institution

University of California San Diego School of Medicine, 214 Dickinson St., Bldg CTF, Rm C102, San Diego, CA 92103-8467, USA. naviaux@ucsd.edu

Source

The Journal of pharmacology and experimental therapeutics 342:3 2012 Sep pg 608-18

MeSH

Animals
Disease
Humans
Immunity, Innate
Metabolic Networks and Pathways
Oxidation-Reduction
Oxidative Stress
Oxygen
Reactive Oxygen Species

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22700427