Preventing Prion Pathogenicity by Targeting the Cellular Prion Protein

Author(s): Andrew J. Nicoll, John Collinge

Journal Name: Infectious Disorders - Drug Targets
Formerly Current Drug Targets - Infectious Disorders

Volume 9 , Issue 1 , 2009

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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

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Article Details

Year: 2009
Page: [48 - 57]
Pages: 10
DOI: 10.2174/1871526510909010048

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