Brain Composition: Age-Related Changes
Alzheimer’s disease (AD) and other age-related diseases including Parkinson’s disease and Down syndrome share characteristics at the cellular and molecular levels: they are associated with transition metal ion-catalyzed oxidative damage to lipids, proteins, and nucleic acids and racemization of the constituent amino acids of the long-lived proteins. Transition metal ion-catalyzed lipid peroxidation leads to the formation of a variety of cellular toxicants such as trans-4-hydroxy-2-nonenal and trans-4-oxo-2-nonenal, which can deplete intracellular levels of glutathione and deactivate enzymes such as glutathione peroxidase. Higher intracellular concentrations of cholesterol and other lipids, under the conditions of oxidative stress, lead to the enhanced formation of amyloid-ß (Aß) peptide in cases of AD. Further, amino acid residues, especially aspartic acid residues in long-lived proteins (e.g., lens crystallin and Aß protein precursor), are prone to accelerated racemization in age-related diseases, forming proteolytically stable, neurotoxic peptides. Cholesterol-lowering drugs (e.g., statins), antioxidants, and metal ion chelators (e.g., clioquinol and desferrioxamine) are potentially promising therapeutics for AD and other age-related diseases.
P. Reddy et al., "Brain Composition: Age-Related Changes," Encyclopedia of Neuroscience, pp. 313-316, Elsevier Ltd, Jan 2010.
The definitive version is available at https://doi.org/10.1016/B978-008045046-9.00108-X
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