Influence of gold nanoparticle surface chemistry and diameter upon Alzheimer's disease amyloid-β protein aggregation.

Background: Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimer's disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aβ aggregation. While a variety of possible aggregation inhibitors have been explored, only nanoparticles (NPs) exhibit promise at low substoichiometric ratios.

Inhibition of amyloid-β aggregation by coumarin analogs can be manipulated by functionalization of the aromatic center.

Aggregation of the amyloid-β protein (Aβ) plays a pathogenic role in the progression of Alzheimer's disease, and small molecules that attenuate Aβ aggregation have been identified toward a therapeutic strategy that targets the disease's underlying cause. Compounds containing aromatic structures have been repeatedly reported as effective inhibitors of Aβ aggregation, but the functional groups that influence inhibition by these aromatic centers have been less frequently explored. The current study identifies analogs of naturally occurring coumarin as novel inhibitors of Aβ aggregation.

Activation of brain endothelium by soluble aggregates of the amyloid-β protein involves nuclear factor-κB.

Cerebrovascular accumulation of amyloid-β protein (Aβ) aggregates in Alzheimer's disease (AD) is proposed to contribute to disease progression and brain inflammation as a result of Aβ-induced increases in endothelial monolayer permeability and stimulation of the endothelium for cellular adhesion and transmigration. These deficiencies facilitate the entry of serum proteins and monocyte-derived microglia into the brain. In the current study, a role for nuclear factor-κB (NF-κB) in the activation of cerebral microvascular endothelial cells by Aβ is explored.

Comparative study of inhibition at multiple stages of amyloid-beta self-assembly provides mechanistic insight.

The "amyloid cascade hypothesis," linking self-assembly of the amyloid-beta protein (Abeta) to the pathogenesis of Alzheimer's disease, has led to the emergence of inhibition of Abeta self-assembly as a prime therapeutic strategy for this currently unpreventable and devastating disease. The complexity of Abeta self-assembly, which involves multiple reaction intermediates related by nonlinear and interconnected nucleation and growth mechanisms, provides multiple points for inhibitor intervention. Although a number of small-molecule inhibitors of Abeta self-assembly have been identified, little insight has been garnered concerning the point at which these inhibitors intervene within the Abeta assembly process.