Implications of protein structure instability: From physiological to pathological secondary structure

Alyona Sukhanova, Simon Poly, Anton Shemetov, Igor Bronstein, Igor Nabiev

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

Proteins are folded during their synthesis; this process may be spontaneous or assisted. Both phenomena are carefully regulated by the " housekeeping" mechanism and molecular chaperones to avoid the appearance of misfolded proteins. Unfolding process generally occurs during physiological degradation of protein, but in some specific cases it results from genetic or environmental changes and does not correspond to metabolic needs. The main outcome of these phenomena is the appearance of nonfunctional pathologically unfolded proteins with a strong tendency to aggregation. Moreover, for some of these unfolded proteins, the agglomeration that follows initial proteins association may give rise to highly structured soluble aggregates. These aggregates have been identified as the main cause of the so-called amyloidosis or amyloid diseases, such as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob diseases, and type II diabetes mellitus. Although some common mechanisms of amyloid protein aggregation have been identified, the roles of the environmental conditions inducing amyloidosis remain to be clarified. In this review, we will summarize recent studies identifying the origin of amyloid nucleation and will try to predict the therapeutic prospects that may be opened by elucidation of the amyloidosis mechanisms.

Original languageEnglish (US)
Pages (from-to)577-588
Number of pages12
JournalBiopolymers
Volume97
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • amyloid
  • amyloidosis
  • proteopathy
  • secondary structure

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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