アミロイドβの構造多型・神経毒性・および凝集制御戦略に関する総説
This review synthesizes multidisciplinary research on amyloid-β (Aβ) oligomeric species, which vary considerably in molecular weight, three-dimensional conformation, and morphology. Aβ assemblies can form through both on-fibrillar and off-fibrillar pathways, and their stability, biological function, and neurotoxic potential differ depending on experimental conditions. Structural integrity of these species is maintained by intramolecular and intermolecular hydrogen bonds alongside electrostatic and hydrophobic forces, all of which are sensitive to environmental parameters such as pH, ionic composition, and solvent, as well as interactions with lipids and proteins. The review is organized into three sections: (1) fibrillar and non-fibrillar assembly mechanisms and Aβ structural polymorphism; (2) how interactions with cellular components and other molecules shape the aggregation pathway; and (3) current inhibitor- and inducer-based strategies targeting specific Aβ oligomeric species to counteract downstream neurotoxic cascades, drawing on both in vitro and preclinical evidence.
Aβ oligomers assemble via on- and off-fibrillar pathways, with structural stability conferred by intramolecular and intermolecular hydrogen bonds, electrostatic interactions, and hydrophobic forces. Environmental factors (pH, ions, solvent) and interactions with lipids and proteins collectively determine the aggregation route and the degree of neurotoxicity.
The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/34643743