Residues 17-20 and 30-35 of Beta-Amyloid Play Critical Roles in Aggregation

Ruitian Liu, Chad McAllister, Yuri Lyubchenko, Michael R. Sierks

Research output: Contribution to journalShort survey

128 Citations (Scopus)

Abstract

We examined the effects of co-incubating nine different Aβ peptide fragments with full-length Aβ1-40 (Aβ40) on protein aggregation. Six fragments enhanced aggregation of Aβ40 (Aβ1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Aβ1-11, 1-16, and 20-29). All of the peptides that enhanced aggregation contained either residues 17-20 or 30-35, indicating the importance of these regions for promoting aggregation of full-length Aβ. Aβ25-35 in particular increased both the rate and extent of aggregation of Aβ40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Aβ25-35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Aβ25-35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Aβ40, along with formation of Aβ25-35 oligomers and thin filaments, represent two different potential pathways for Aβ25-35 toxicity. The critical roles of residues 17-20 and 30-35 of Aβ provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of β-sheet breakers to modulate the aggregation and inhibit toxicity of full-length Aβ.

Original languageEnglish (US)
Pages (from-to)162-171
Number of pages10
JournalJournal of Neuroscience Research
Volume75
Issue number2
DOIs
StatePublished - Jan 15 2004

Fingerprint

Poisons
Amyloid
Fluorescence
Staining and Labeling
Peptide Fragments
Alzheimer Disease
Peptides
Proteins

Keywords

  • Alzheimer's disease (AD)
  • Atomic Force Microscope (AFM), cytotoxicity
  • Thioflavin T (ThT)
  • β-amyloid (Aβ)
  • β-amyloid 25-35 (Aβ25-35)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Residues 17-20 and 30-35 of Beta-Amyloid Play Critical Roles in Aggregation. / Liu, Ruitian; McAllister, Chad; Lyubchenko, Yuri; Sierks, Michael R.

In: Journal of Neuroscience Research, Vol. 75, No. 2, 15.01.2004, p. 162-171.

Research output: Contribution to journalShort survey

Liu, Ruitian ; McAllister, Chad ; Lyubchenko, Yuri ; Sierks, Michael R. / Residues 17-20 and 30-35 of Beta-Amyloid Play Critical Roles in Aggregation. In: Journal of Neuroscience Research. 2004 ; Vol. 75, No. 2. pp. 162-171.
@article{1f4574ddb14548fc88c8cf4821169333,
title = "Residues 17-20 and 30-35 of Beta-Amyloid Play Critical Roles in Aggregation",
abstract = "We examined the effects of co-incubating nine different Aβ peptide fragments with full-length Aβ1-40 (Aβ40) on protein aggregation. Six fragments enhanced aggregation of Aβ40 (Aβ1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Aβ1-11, 1-16, and 20-29). All of the peptides that enhanced aggregation contained either residues 17-20 or 30-35, indicating the importance of these regions for promoting aggregation of full-length Aβ. Aβ25-35 in particular increased both the rate and extent of aggregation of Aβ40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Aβ25-35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Aβ25-35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Aβ40, along with formation of Aβ25-35 oligomers and thin filaments, represent two different potential pathways for Aβ25-35 toxicity. The critical roles of residues 17-20 and 30-35 of Aβ provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of β-sheet breakers to modulate the aggregation and inhibit toxicity of full-length Aβ.",
keywords = "Alzheimer's disease (AD), Atomic Force Microscope (AFM), cytotoxicity, Thioflavin T (ThT), β-amyloid (Aβ), β-amyloid 25-35 (Aβ25-35)",
author = "Ruitian Liu and Chad McAllister and Yuri Lyubchenko and Sierks, {Michael R.}",
year = "2004",
month = "1",
day = "15",
doi = "10.1002/jnr.10859",
language = "English (US)",
volume = "75",
pages = "162--171",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Residues 17-20 and 30-35 of Beta-Amyloid Play Critical Roles in Aggregation

AU - Liu, Ruitian

AU - McAllister, Chad

AU - Lyubchenko, Yuri

AU - Sierks, Michael R.

PY - 2004/1/15

Y1 - 2004/1/15

N2 - We examined the effects of co-incubating nine different Aβ peptide fragments with full-length Aβ1-40 (Aβ40) on protein aggregation. Six fragments enhanced aggregation of Aβ40 (Aβ1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Aβ1-11, 1-16, and 20-29). All of the peptides that enhanced aggregation contained either residues 17-20 or 30-35, indicating the importance of these regions for promoting aggregation of full-length Aβ. Aβ25-35 in particular increased both the rate and extent of aggregation of Aβ40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Aβ25-35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Aβ25-35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Aβ40, along with formation of Aβ25-35 oligomers and thin filaments, represent two different potential pathways for Aβ25-35 toxicity. The critical roles of residues 17-20 and 30-35 of Aβ provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of β-sheet breakers to modulate the aggregation and inhibit toxicity of full-length Aβ.

AB - We examined the effects of co-incubating nine different Aβ peptide fragments with full-length Aβ1-40 (Aβ40) on protein aggregation. Six fragments enhanced aggregation of Aβ40 (Aβ1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Aβ1-11, 1-16, and 20-29). All of the peptides that enhanced aggregation contained either residues 17-20 or 30-35, indicating the importance of these regions for promoting aggregation of full-length Aβ. Aβ25-35 in particular increased both the rate and extent of aggregation of Aβ40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Aβ25-35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Aβ25-35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Aβ40, along with formation of Aβ25-35 oligomers and thin filaments, represent two different potential pathways for Aβ25-35 toxicity. The critical roles of residues 17-20 and 30-35 of Aβ provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of β-sheet breakers to modulate the aggregation and inhibit toxicity of full-length Aβ.

KW - Alzheimer's disease (AD)

KW - Atomic Force Microscope (AFM), cytotoxicity

KW - Thioflavin T (ThT)

KW - β-amyloid (Aβ)

KW - β-amyloid 25-35 (Aβ25-35)

UR - http://www.scopus.com/inward/record.url?scp=0346099098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346099098&partnerID=8YFLogxK

U2 - 10.1002/jnr.10859

DO - 10.1002/jnr.10859

M3 - Short survey

C2 - 14705137

AN - SCOPUS:0346099098

VL - 75

SP - 162

EP - 171

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 2

ER -