Effect of aldehydes derived from oxidative deamination and oxidative stress on beta-amyloid aggregation; pathological implications to Alzheimer's disease.
Formaldehyde and methylglyoxal are generated via deamination from methylamine and aminoacetone respectively catalyzed by semicarbazide-sensitive amine oxidase (SSAO). Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are end products of lipid peroxidation due to oxidative stress. These aldehydes are capable of inducing protein cross-linkage. Elevated levels of aldehydes were found in Alzheimer's disease (AD). These reactive metabolites may potentially play important roles in beta-amyloid (Abeta) aggregation related to the pathology of AD. In the present study thioflavin-T (ThT) fluorometry, an immuno-dot-blot assay and atomic force microscopy (AFM) were employed to reveal the effect of aldehydes on Abeta aggregation in vitro. The target on Abeta for interaction with formaldehyde was identified. The results support the involvement of endogenous aldehydes in amyloid deposition related to AD.
Chen
K
K
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Kazachkov
M
M
Yu
P H
PH
D000447:Aldehydes / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D003641:Deamination; D005557:Formaldehyde / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D058225:Plaque, Amyloid / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D005557:Formaldehyde; D008315:Malondialdehyde; D011765:Pyruvaldehyde; C027576:4-hydroxy-2-nonenal