Interplay between protein homeostasis networks in protein aggregation and proteotoxicity

Peter M. Douglas, Douglas M. Cyr

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

The misfolding and aggregation of disease proteins is characteristic of numerous neurodegenerative diseases. Particular neuronal populations are more vulnerable to proteotoxicity while others are more apt to tolerate the misfolding and aggregation of disease proteins. Thus, the cellular environment must play a signi.cant role in determining whether disease proteins are converted into toxic or benign forms. The endomembrane network of eukaryotes divides the cell into different subcellular compartments that possess distinct sets of molecular chaperones and protein interaction networks. Chaperones act as agonists and antagonists of disease protein aggregation to prevent the accumulation of toxic intermediates in the aggregation pathway. Interacting partners can also modulate the conformation and localization of disease proteins and thereby in.uence proteotoxicity. Thus, interplay between these protein homeostasis network components can modulate the selfassociation of disease proteins and determine whether they elicit a toxic or benign outcome.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalBiopolymers
Volume93
Issue number3
DOIs
StatePublished - Feb 3 2010

Fingerprint

Homeostasis
Agglomeration
Poisons
Proteins
Proteostasis Deficiencies
Protein Interaction Maps
Molecular Chaperones
Vulnerable Populations
Eukaryota
Neurodegenerative Diseases
Neurodegenerative diseases
Network components
Conformations

Keywords

  • Molecular chaperones
  • Protein aggregation
  • Protein misfolding

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

Cite this

Interplay between protein homeostasis networks in protein aggregation and proteotoxicity. / Douglas, Peter M.; Cyr, Douglas M.

In: Biopolymers, Vol. 93, No. 3, 03.02.2010, p. 229-236.

Research output: Contribution to journalReview article

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