What is the role of protein aggregation in neurodegeneration?

Christopher A Ross, Michelle A. Poirier

Research output: Contribution to journalArticle

Abstract

Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.

Original languageEnglish (US)
Pages (from-to)891-898
Number of pages8
JournalNature Reviews Molecular Cell Biology
Volume6
Issue number11
DOIs
StatePublished - Nov 2005

Fingerprint

Inclusion Bodies
Neurodegenerative Diseases
Proteins
Poisons
Carbon Monoxide
Hydrogen
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

What is the role of protein aggregation in neurodegeneration? / Ross, Christopher A; Poirier, Michelle A.

In: Nature Reviews Molecular Cell Biology, Vol. 6, No. 11, 11.2005, p. 891-898.

Research output: Contribution to journalArticle

@article{b7f88972c404455badd33b0996ec7208,
title = "What is the role of protein aggregation in neurodegeneration?",
abstract = "Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.",
author = "Ross, {Christopher A} and Poirier, {Michelle A.}",
year = "2005",
month = "11",
doi = "10.1038/nrm1742",
language = "English (US)",
volume = "6",
pages = "891--898",
journal = "Nature Reviews Molecular Cell Biology",
issn = "1471-0072",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - What is the role of protein aggregation in neurodegeneration?

AU - Ross, Christopher A

AU - Poirier, Michelle A.

PY - 2005/11

Y1 - 2005/11

N2 - Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.

AB - Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.

UR - http://www.scopus.com/inward/record.url?scp=27644596641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644596641&partnerID=8YFLogxK

U2 - 10.1038/nrm1742

DO - 10.1038/nrm1742

M3 - Article

C2 - 16167052

AN - SCOPUS:27644596641

VL - 6

SP - 891

EP - 898

JO - Nature Reviews Molecular Cell Biology

JF - Nature Reviews Molecular Cell Biology

SN - 1471-0072

IS - 11

ER -