Physical and toxicological profiles of human IAPP amyloids and plaques

Aleksandr Kakinen, Yunxiang Sun, Ibrahim Javed, Ava Faridi, Emily H Pilkington, Pouya Faridi, Anthony W Purcell, Ruhong Zhou, Feng Ding, Sijie Lin, Pu Chun Ke , Thomas P Davis

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide (IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model. The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication, which displayed comparable stiffness but age-dependent fragmentation, followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date. The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active, long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases.

Original languageEnglish
Pages (from-to)26-35
Number of pages10
JournalScience Bulletin
Volume64
Issue number1
DOIs
Publication statusPublished - 15 Jan 2019

Keywords

  • Amyloid
  • IAPP
  • Plaque
  • Self assembly
  • Toxicity

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