The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases.
Published
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
Language
- eng
Conference Location
- Egypt