Effect of agitation on the peptide fibrillization: Alzheimer's amyloid-β peptide 1-42 but not amylin and insulin fibrils can grow under quiescent conditions

• Published in: Journal of peptide science Vol. 19; no. 6; pp. 386 - 391
• Main Authors: Tiiman, Ann, Noormägi, Andra, Friedemann, Merlin, Krishtal, Jekaterina, Palumaa, Peep, Tõugu, Vello
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2013
• Subjects: agitation; Alzheimer Disease; Alzheimer's amyloid-β; amylin; Amyloid - chemistry; Amyloid beta-Peptides - chemistry; fibrillization; insulin; Insulin - chemistry; Islet Amyloid Polypeptide - chemistry; Peptide Fragments - chemistry
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2513

Many peptides and proteins can form fibrillar aggregates in vitro, but only a limited number of them are forming pathological amyloid structures in vivo. We studied the fibrillization of four peptides – Alzheimer's amyloid‐β (Aβ) 1‐40 and 1‐42, amylin and insulin. In all cases, intensive mechanical agitation of the solution initiated fast fibrillization. However, when the mixing was stopped during the fibril growth phase, the fibrillization of amylin and insulin was practically stopped, and the rate for Aβ40 substantially decreased, whereas the fibrillization of Aβ42 peptide continued to proceed with almost the same rate as in the agitated conditions. The reason for the different sensitivity of the in vitro fibrillization of these peptides towards agitation in the fibril growth phase remains elusive. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. In this paper, the effect of stirring on the fibrillization of three peptides was studied. When stirring is stopped, the fibrillization of amylin and insulin practically stopped, and the rate for Aβ40 substantially decreased, whereas the fibrillization of Aβ42 peptide continued to proceed with almost the same rate as in the agitated conditions. This ability of Aβ42 fibrils to grow under quiescent conditions could be responsible for their high propensity to form pathological aggregates in vivo.