Distinct functional diversity of branched oligosaccharides as chaperones and inhibitory-binding partners of amyloid beta-protein and its aggregates.

Aggregation and deposition of amyloid beta-protein 1-42 (Aβ42) in the brain, primarily owing to hydrophobic interactions between Aβ42 chains, is a common pathology in all forms of Alzheimer's disease (AD). Hydrophilic oligosaccharides are widely present in the extracellular matrix and on the cytoplasmic membrane. To determine if oligosaccharides bind to Aβ42 or its aggregates and consequently affect their aggregation and cellular function, this study examined the interaction of typical functional oligosaccharides with Aβ42 or its aggregates.

Synergetic effect of matrine on the catalytic scFv antibody HS72 in vitro and in mice with Alzheimer disease pathology.

Single-chain variable fragment (scFv) HS72 is a catalytic antibody that specifically degrades amyloid β-protein 1-42 (Aβ42) aggregates in vitro or reduces the level or burden of Aβ42 deposits/plaques in the brains of mice with Alzheimer disease pathology. Its efficacy has been shown in protecting neural cells in vitro and improving the morphology of the cell population in the brain of mice with AD pathology (AD mice). Matrine (Mat) is a natural product capable of binding to Aβ42 or its aggregates and blocking their neurotoxicity at concentrations of at least 10 μM or greater.

Dual Efficacy of a Catalytic Anti-Oligomeric Aβ42 scFv Antibody in Clearing Aβ42 Aggregates and Reducing Aβ Burden in the Brains of Alzheimer's Disease Mice.

One of the primary pathological mechanisms underlying Alzheimer's disease (AD) is the deposition of amyloid β-protein (Aβ42) aggregates in the brain. In this study, a catalytic anti-oligomeric Aβ42 scFv antibody, HS72, was identified by screening a human antibody library, its ability to degrade Aβ42 aggregates was defined, and its role in the reduction of Aβ burden in the AD mouse brain was evaluated. HS72 specifically targeted Aβ42 aggregates with an approximately 14-68 kDa range.

Extracellular Amyloid β-protein (1-42) Oligomers Anchor Brain Cells and Make them inert as an Unconventional Integrin-Coupled Ligand.

This study aimed to investigate the effect of extracellular Aβ42 on neural cell migration, and the possible molecular mechanisms. Extracellular Aβ42 monomers did not negatively affect the motility of neural cells; however, they could promote cell migration from toxic extracellular Aβ42 oligomers. Contrastingly, extracellular Aβ42 aggregates, especially Aβ42 oligomers, significantly decreased neural cell migration while reducing their survival.