Mechanisms of prion protein aggregation

Sarah N Fontaine, David R Brown

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The prion protein is a cell surface glycoprotein that is converted to a protease resistant abnormal isoform during the course of prion disease. The normal isoform of this protein has been shown to be an antioxidant that aids the survival of neurones. The abnormal isoform is associated with both the transmissible agent of prion diseases and is also toxic. Recent studies have shown that there are multiple end states in terms of aggregation of the protein. Both soluble oligomers and insoluble fibrils can form from the abnormal isoform. Although fibrils are characteristic of the disease, the most infectious prions are associated with oligomers. Neurotoxicity can be associated with fibrils but mostly appears to be due to small aggregates. For many years fibrils were believed to be central to the disease process but currently evidence supports the notion that fibrils represent a "bulk" form of abnormal protein, which is largely inert, but carried along a small active component. This review will examine what is known about the mechanisms behind prion protein aggregation, and the relevance of each form for the disease.
Original languageEnglish
Pages (from-to)14-26
Number of pages13
JournalProtein and Peptide Letters
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Protein Isoforms
Agglomeration
Prions
Prion Diseases
Oligomers
Poisons
Membrane Glycoproteins
Communicable Diseases
Proteins
Peptide Hydrolases
Antioxidants
Neurons
Prion Proteins

Keywords

  • aggregation
  • structure
  • neurotoxicity
  • Prion
  • oligomer
  • fibril

Cite this

Mechanisms of prion protein aggregation. / Fontaine, Sarah N; Brown, David R.

In: Protein and Peptide Letters, Vol. 16, No. 1, 01.2009, p. 14-26.

Research output: Contribution to journalArticle

Fontaine, Sarah N ; Brown, David R. / Mechanisms of prion protein aggregation. In: Protein and Peptide Letters. 2009 ; Vol. 16, No. 1. pp. 14-26.
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