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

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

Cite this

Kakinen, Aleksandr ; Sun, Yunxiang ; Javed, Ibrahim ; Faridi, Ava ; Pilkington, Emily H ; Faridi, Pouya ; Purcell, Anthony W ; Zhou, Ruhong ; Ding, Feng ; Lin, Sijie ; Ke , Pu Chun ; Davis, Thomas P. / Physical and toxicological profiles of human IAPP amyloids and plaques. In: Science Bulletin. 2019 ; Vol. 64, No. 1. pp. 26-35.
@article{2782ed84891f4d9bb1f14d11f7f816da,
title = "Physical and toxicological profiles of human IAPP amyloids and plaques",
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.",
keywords = "Amyloid, IAPP, Plaque, Self assembly, Toxicity",
author = "Aleksandr Kakinen and Yunxiang Sun and Ibrahim Javed and Ava Faridi and Pilkington, {Emily H} and Pouya Faridi and Purcell, {Anthony W} and Ruhong Zhou and Feng Ding and Sijie Lin and Ke, {Pu Chun} and Davis, {Thomas P}",
year = "2019",
month = "1",
day = "15",
doi = "10.1016/j.scib.2018.11.012",
language = "English",
volume = "64",
pages = "26--35",
journal = "Science Bulletin",
issn = "2095-9273",
publisher = "Elsevier",
number = "1",

}

Physical and toxicological profiles of human IAPP amyloids and plaques. / Kakinen, Aleksandr; Sun, Yunxiang; Javed, Ibrahim; Faridi, Ava; Pilkington, Emily H; Faridi, Pouya; Purcell, Anthony W; Zhou, Ruhong; Ding, Feng; Lin, Sijie; Ke , Pu Chun ; Davis, Thomas P.

In: Science Bulletin, Vol. 64, No. 1, 15.01.2019, p. 26-35.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Physical and toxicological profiles of human IAPP amyloids and plaques

AU - Kakinen, Aleksandr

AU - Sun, Yunxiang

AU - Javed, Ibrahim

AU - Faridi, Ava

AU - Pilkington, Emily H

AU - Faridi, Pouya

AU - Purcell, Anthony W

AU - Zhou, Ruhong

AU - Ding, Feng

AU - Lin, Sijie

AU - Ke , Pu Chun

AU - Davis, Thomas P

PY - 2019/1/15

Y1 - 2019/1/15

N2 - 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.

AB - 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.

KW - Amyloid

KW - IAPP

KW - Plaque

KW - Self assembly

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=85058459283&partnerID=8YFLogxK

U2 - 10.1016/j.scib.2018.11.012

DO - 10.1016/j.scib.2018.11.012

M3 - Article

VL - 64

SP - 26

EP - 35

JO - Science Bulletin

JF - Science Bulletin

SN - 2095-9273

IS - 1

ER -