Environmental-induced oxidative stress in neurodegenerative disorders and aging

Abstract

The aetiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. Free radicals derived primarily from molecular oxygen have been implicated and considered as associated risk factors for a variety of human disorders including neurodegenerative diseases and aging. Damage to tissue biomolecules, including lipids, proteins and DNA, by free radicals is postulated to contribute importantly to the pathophysiology of oxidative stress. The potential of environmental exposure to metals, air pollution and pesticides as well as diet as risk factors via the induction of oxidative stress for neurodegenerative diseases and aging is discussed. The role of genetic background is discussed on the light of the oxidative stress implication, focusing on both complex neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis) and monogenic neurological disorders (Huntington's disease, Ataxia telangiectasia, Friedreich Ataxia and others). Emphasis is given to role of the repair mechanisms of oxidative DNA damage in delaying aging and protecting against neurodegeneration. The emerging interplay between environmental-induced oxidative stress and epigenetic modifications of critical genes for neurodegeneration is also discussed.