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.
Keywords: Prion, aggregation, fibril, oligomer, structure, neurotoxicity
Protein & Peptide Letters
Title: Mechanisms of Prion Protein Aggregation
Volume: 16 Issue: 1
Author(s): Sarah N. Fontaine and David R. Brown
Affiliation:
Keywords: Prion, aggregation, fibril, oligomer, structure, neurotoxicity
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.
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Cite this article as:
Fontaine N. Sarah and Brown R. David, Mechanisms of Prion Protein Aggregation, Protein & Peptide Letters 2009; 16 (1) . https://dx.doi.org/10.2174/092986609787049411
DOI https://dx.doi.org/10.2174/092986609787049411 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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