Abstract
Prions are unique in that the infectious particles contain no detectable nucleic acid and appear to consist of aggregated forms of misfolded cellular prion protein. Prions form distinct strains and can transmit disease between species. Whilst the molecular basis of prion diseases is beginning to be unravelled, much remains unknown including the atomic structure of the infectious and toxic species. In contrast, the structure and folding properties of the cellular prion protein are well characterised and, although its precise function remains enigmatic, constitutive knockout of protein expression in mice produces apparently healthy animals but which are fully resistant to prion infection. Furthermore, recent data show that neuronal knockout of the gene encoding for prion protein during established brain infection leads to reversal of pathology and behavioural deficits, giving hope that effective therapies could be designed. Stabilising the cellular form of the prion protein and preventing it from misfolding could be one way to slow or prevent prion formation. Immunotherapy of peripherally prion-infected mice with an antibody specific for cellular prion protein can prevent disease onset. However, a small molecule capable of curing prion infection in vivo has still to be discovered. Recent work has provided proof of principle that compounds which bind selectively to the cellular prion protein could act as therapeutics for prion diseases.
Keywords: Prion protein, prion disease, therapeutics, high throughput screening, mass action, ligand binding
Infectious Disorders - Drug Targets
Title: Preventing Prion Pathogenicity by Targeting the Cellular Prion Protein
Volume: 9 Issue: 1
Author(s): Andrew J. Nicoll and John Collinge
Affiliation:
Keywords: Prion protein, prion disease, therapeutics, high throughput screening, mass action, ligand binding
Abstract: Prions are unique in that the infectious particles contain no detectable nucleic acid and appear to consist of aggregated forms of misfolded cellular prion protein. Prions form distinct strains and can transmit disease between species. Whilst the molecular basis of prion diseases is beginning to be unravelled, much remains unknown including the atomic structure of the infectious and toxic species. In contrast, the structure and folding properties of the cellular prion protein are well characterised and, although its precise function remains enigmatic, constitutive knockout of protein expression in mice produces apparently healthy animals but which are fully resistant to prion infection. Furthermore, recent data show that neuronal knockout of the gene encoding for prion protein during established brain infection leads to reversal of pathology and behavioural deficits, giving hope that effective therapies could be designed. Stabilising the cellular form of the prion protein and preventing it from misfolding could be one way to slow or prevent prion formation. Immunotherapy of peripherally prion-infected mice with an antibody specific for cellular prion protein can prevent disease onset. However, a small molecule capable of curing prion infection in vivo has still to be discovered. Recent work has provided proof of principle that compounds which bind selectively to the cellular prion protein could act as therapeutics for prion diseases.
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Cite this article as:
Nicoll J. Andrew and Collinge John, Preventing Prion Pathogenicity by Targeting the Cellular Prion Protein, Infectious Disorders - Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/1871526510909010048
DOI https://dx.doi.org/10.2174/1871526510909010048 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
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New Frontiers in Infectious Disease Research: Small-Molecule Probes and Biomarker Identification
The biological relevance of small-molecule chemical probes targeting a disease model is crucial in the early stages of drug discovery. The integration of omics technologies such as genomics, proteomics, metabolomics, immunomic, and cellular levels has greatly enhanced the ability to identify novel biomarkers and understand the complex interactions between pathogens ...read more

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