1,5‐Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid‐β(1‐40) Fibrillization

Oxidative Stress: 1,5‐Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid‐β(1‐40) Fibrillization (Adv. Sci. 10/2016)

Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane forma...

Alzheimer’s amyloid-β A2T variant and its N-terminal peptides inhibit amyloid-β fibrillization and rescue the induced cytotoxicity

Alzheimer's disease (AD) is the most common dementia affecting tens of million people worldwide. The primary neuropathological hallmark in AD is amyloid plaques composed of amyloid-β peptide (Aβ). Several familial mutations found in Aβ sequence result in early onset of AD. Previous studies showed that the mutations located at N-terminus of Aβ, such as the English (H6R) and Tottori (D7N) mutatio...

Negatively charged gold nanoparticles inhibit Alzheimer's amyloid-β fibrillization, induce fibril dissociation, and mitigate neurotoxicity.

Amyloids are pathogenic hallmarks in many neurodegenerative diseases such as amyloid-β (Aβ) fibrils in Alzheimer's disease (AD). Here, the effect of gold nanoparticles (AuNPs) on amyloids is examined using Aβ as a model system. It is found that bare AuNPs inhibited Aβ fibrillization to form fragmented fibrils and spherical oligomers. Adding bare AuNPs to preformed Aβ fibrils results in ragged s...

Inhibitory Effect of Curcumin-Cu(II) and Curcumin-Zn(II) Complexes on Amyloid-Beta Peptide Fibrillation

Mononuclear complexes of Curcumin with Cu(II) and Zn(II) have been synthesized and, characterized and their effects on the fibrillization and aggregation of amyloid-beta (Aβ) peptide have been studied. FTIR spectroscopy and atomic force microscopy (AFM) observations demonstrate that the complexes can inhibit the transition from less structured oligomers to β-sheet rich protofibrils which act as...