title: Carbonyl toxicology and Alzheimer's disease.
abstract: A large amount of data has implicated reactive carbonyls as neurotoxic mediators of oxidative damage in the progression of Alzheimer's disease (AD) and other neurodegenerative diseases. The oxidation of polyunsaturated fatty acids, reducing sugars, and amino acids leads to the formation of carbonyls and carbonyl adduction products such as 4-hydroxy-2-nonenal (HNE), advanced glycation end products (AGEs), and protein-bound carbonyls. Levels of these products are elevated in AD. In this review, we examine the role that carbonyls may play in the development of this disease. We focus upon the chemistry of these molecules and the evidence for their involvement in AD. The biological effects of these carbonyl species in model systems and their relationship to AD are discussed. Lastly, we examine the potential mechanisms that the brain utilizes to detoxify carbonyl species and possible therapeutic interventions based on carbonyl detoxification.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Science, Grand Forks 58203, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Picklo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Amarnath
authors.forename: M Diana
authors.initials: MD
authors.lastname: Neely
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000596:Amino Acids; D017127:Glycation End Products, Advanced; D016875:tau Proteins; C027576:4-hydroxy-2-nonenal