Structure Comparison of Beta Amyloid Peptide Aβ 1-42 Isoforms. Molecular Dynamics Modeling.

Beta amyloid peptide Aβ 1-42 (Aβ42) has a unique dual role in the human organism, as both the peptide with an important physiological function and one of the most toxic biological compounds provoking Alzheimer's disease (AD). There are several known Aβ42 isoforms that we discuss here that are highly neurotoxic and lead to the early onset of AD. Aβ42 is an intrinsically disordered protein with no experimentally solved structure under physiological conditions.

Molecular Mechanism of Zinc-Dependent Oligomerization of Alzheimer's Amyloid-β with Taiwan (D7H) Mutation.

Amyloid-β (Aβ) is a peptide formed by 39-43 amino acids, heterogenous by the length of its C-terminus. Aβ constitutes a subnanomolar monomeric component of human biological fluids; however, in sporadic variants of Alzheimer's disease (AD), it forms soluble neurotoxic oligomers and accumulates as insoluble extracellular polymeric aggregates (amyloid plaques) in the brain tissues. The plaque formation is controlled by zinc ions; therefore, abnormal interactions between the ions and Aβ seem to take part in the triggering of sporadic AD.

Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.

The pathogenesis of Alzheimer's disease (AD) is associated with the formation of cerebral amyloid plaques, the main components of which are the modified Aβ molecules as well as the metal ions. Aβ isomerized at Asp7 residue (isoD7-Aβ) is the most abundant isoform in amyloid plaques. We hypothesized that the pathogenic effect of isoD7-Aβ is due to the formation of zinc-dependent oligomers, and that this interaction can be disrupted by the rationally designed tetrapeptide (HAEE).

Docking and Molecular Dynamics-Based Identification of Interaction between Various Beta-Amyloid Isoforms and RAGE Receptor.

Beta-amyloid peptide (Aβ) is a ligand associated with RAGE (Advanced glycosylation end product-specific receptor). Aβ is translocated in complexes with RAGE from the blood to brain across the blood-brain barrier (BBB) by transcytosis. Aβ and its isoforms are important factors in the Alzheimer's disease (AD) pathogenesis.