Cell Biochemistry and Biophysics

, Volume 69, Issue 2, pp 275–281 | Cite as

A Model for Small Heat Shock Protein Inhibition of Polyglutamine Aggregation

Original Paper

Abstract

Polyglutamine (polyQ) repeat expansions that lead to the formation of amyloid aggregates are linked to several devastating neurodegenerative disorders. While molecular chaperones, including the small heat shock proteins (sHsp), play an important role in protection against protein misfolding, the aberrant protein folding that accompanies these polyQ diseases overwhelms the chaperone network. By generating a model structure to explain the observed suppression of spinocerebellar ataxia 3 (SCA3) by the sHsp αB-crystallin, we have identified key vulnerabilities that provide a possible mechanism to explain this heat shock response. A docking study involving a small bioactive peptide should also aid in the development of new drug targets for the prevention of polyQ-based aggregation.

Keywords

αB-crystallin Small heat shock proteins SHsp Ataxin-3 PolyQ Spinocerebellar ataxia Fibrillar aggregation 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Eamonn F. Healy
    • 1
  • Carley Little
    • 1
  • Peter J. King
    • 2
  1. 1.Department of ChemistrySt. Edward’s UniversityAustinUSA
  2. 2.Department of Biological SciencesSt. Edward’s UniversityAustinUSA

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