Neuronal vulnerability to oxidative damage in aging

E. Okun, Mark P. Mattson

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The aging process in the brain is as robust as it is in other body organs and manifests as decrements in cognition, sensory and motor abilities, and autonomic control of various organ systems. This is due to the fact that, with advancing age, brain cells are exposed to increasing levels of oxidative stress, disturbed energy homeostasis, and accumulation of damage to protein, lipids, and nucleic acids. While these changes occur during normal aging, they are exacerbated in neurons that are susceptible to neurodegenerative disorders. The final outcome of the balance between a person's own genetic background and the environmental changes that affect him or her determines if and when a neurodegenerative disorder will occur. Oxidative molecular alterations that occur during normal aging and that are amplified in the neurons that are affected in neurodegenerative disorders include protein nitrosylation, oxidation of amino acids and DNA bases, lipid peroxidation, and increased amounts of neurotoxic amino acid derivates such as homocysteine. Oxidative damage may render neurons vulnerable to metabolic stress, excitotoxicity, and apoptosis in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Oxidative stress contributes to the abnormal protein aggregations specific to each disorder − amyloid β-peptide (Aβ) in AD, α-synuclein in PD, huntingtin in HD, and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) in ALS. These protein inclusions may arise, in part, from impaired proteasome function and autophagy. Although the utility of antioxidant ingestion as a preventative strategy for age-related neurological disorders has not yet been demonstrated, age- and disease-related oxidative damage to neurons can be decreased by dietary energy restriction and exercise and accelerated by overeating and diabetes.
Original languageAmerican English
Title of host publicationOxidative Neural Injury
EditorsSigrid C. Veasey
PublisherHumana Press
ISBN (Print)978-1-60327-342-8
StatePublished - 2009

Publication series

NameContemporary Clinical Neuroscience


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