RT Journal Article SR Electronic T1 Remarked Suppression of Aβ42 Protomer-Protomer Dissociation Reaction via Pentamer Dimerization JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.12.431048 DO 10.1101/2021.02.12.431048 A1 Ikuo Kurisaki A1 Shigenori Tanaka YR 2021 UL http://biorxiv.org/content/early/2021/04/07/2021.02.12.431048.abstract AB Amyloid fibril growth is supposed to be common pathogenic causes for neurodegenerative diseases. This process is triggered by accumulation of fibril-like aggregates, while the minimum size of such aggregates still remains to be elucidated. We addressed this problem with employing atomistic molecular dynamics simulations for the paradigmatic amyloid protein, amyloid-β (1-42) (Aβ42). Seven different dimeric forms of oligomeric Aβ42 fibril-like aggregate in aqueous solution, ranging from tetramer to decamer, were considered. We found effects of the size of these fibril-like aggregates on their thermodynamic stability and have clarified kinetic suppression of protomer-protomer dissociation reactions even at the point of pentamer dimer formation, where the theoretically estimated reaction time exceeds lifetime of human beings. Recalling that Aβ42 pentamer is found in the range of size of experimentally-observed Aβ42 aggregates, we could suppose that stable formation of fibril-like Aβ42 pentamer species is involved in a turning point where rapid growth of Aβ42 amyloid fibrils is triggered.Competing Interest StatementThe authors have declared no competing interest.