title: Oxidative stress in neurodegenerative diseases.
abstract: Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2 (-)) and hydroxyl radical (OH(-)), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Manitoba, Canada.
authors.forename: Xueping
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Hebei North University, Zhangjiakou 075000, Hebei Province, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Manitoba, Canada.
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
keywords: neurodegenerative diseases; oxidative stress; reactive oxygen species; reviews; therapy