期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 37, 期 1, 页码 9-18出版社
IOS PRESS
DOI: 10.3233/JAD-122389
关键词
Alzheimer's disease; amyloid-beta; atomic force microscopy; fibrillization; oxidative stress
资金
- National Institutes of Health [NIH R01 AG026151, NIH R01 AG027853]
- NATIONAL INSTITUTE ON AGING [R01AG027853, R01AG026151] Funding Source: NIH RePORTER
Oxidative stress and amyloid-beta (A beta) formation are important processes that occur in Alzheimer's disease (AD). Amyloid formation is associated with the aggregation and precipitation of the A beta peptide, while oxidative stress results from an imbalance in pro-oxidant/antioxidant homeostasis that produces harmful reactive oxygen species. The methionine-35 (Met35) residue of the A beta peptide plays an important role in AD oxidative stress events and the associated neurotoxicity. We and other research groups previously demonstrated that in vitro oxidation of the Met35 side-chain to the sulfoxide (Met35(red) -> Met35(ox)) impedes assembly and aggregation of monomeric A beta peptide into protofibrils, the latter being the immediate precursors of amyloid plaques. Here, we report that Met35 oxidation state affects the stability of preexisting amyloid fibrils and plaques, where the Met35(red) -> Met35(ox) process leads to changes in the morphology of filaments, protofibrils, mature fibrils, and loss of Congo red birefringence in senile plaques isolated from the brains of AD patients. The most notable differences were in fibril flexibility, as evidenced by changes from straight fibrils to irregularly shaped, rope-like fibrils. These findings suggest that the Met35 oxidation state and amyloid plaque formation may be intimately linked.
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