The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases.


Journal Article

Misfolding and abnormal aggregation of proteins in the brain are implicated in the pathogenesis of various neurodegenerative diseases including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. In the polyQ diseases, an abnormally expanded polyQ stretch triggers misfolding and aggregation of the disease-causing proteins, eventually resulting in neurodegeneration. In this paper, we introduce our therapeutic strategy against the polyQ diseases using polyQ binding peptide 1 (QBP1), a peptide that we identified by phage display screening. We showed that QBP1 specifically binds to the expanded polyQ stretch and inhibits its misfolding and aggregation, resulting in suppression of neurodegeneration in cell culture and animal models of the polyQ diseases. We further demonstrated the potential of protein transduction domains (PTDs) for in vivo delivery of QBP1. We hope that in the near future, chemical analogues of aggregation inhibitor peptides including QBP1 will be developed against protein misfolding-associated neurodegenerative diseases.

Full Text

Duke Authors

Cited Authors

  • Popiel, HA; Burke, JR; Strittmatter, WJ; Oishi, S; Fujii, N; Takeuchi, T; Toda, T; Wada, K; Nagai, Y

Published Date

  • 2011

Published In

Volume / Issue

  • 2011 /

Start / End Page

  • 265084 -

PubMed ID

  • 22312459

Pubmed Central ID

  • 22312459

Electronic International Standard Serial Number (EISSN)

  • 2090-0112

Digital Object Identifier (DOI)

  • 10.4061/2011/265084


  • eng

Conference Location

  • Egypt