Abstract
The transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. Many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. However, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. There is increasing pressure to find effective decontaminants for blood supplies, as variant Creutzfeldt Jakob Disease (vCJD) has been shown to be transmissible by blood, and to find non-toxic preventative therapies, with ongoing cases of Bovine Spongiform Encephalopathy (BSE) and the spread of Chronic Wasting Disease (CWD). Within the realm of chemotherapeutic approaches, much research has focussed on blocking the conversion of the normal form of prion protein (PrPc) to its abnormal counterpart (PrPres). Structurally, these chemotherapeutic agents are often polyanionic or polycyclic and may directly bind PrPc or PrPres, or act by redistributing, sequestering, or downregulating PrPc, thus preventing its conversion. There are also some polycationic compounds which proport to enhance the clearance of PrPres. Other targets include accessory molecules such as the laminin receptor precursor which influences conversion, or cell signalling molecules which may be required for pathogenesis. Of recent interest are the possible neuroprotective effects of some drugs. Importantly, there is evidence that combining compounds may provide synergistic responses. This review provides an update on current testing methods, therapeutic targets, and promising candidates for chemical-based therapy.
Keywords: Prion, PrP, chemotherapeutic, decontamination, prophylaxis, polyanion, conversion
Infectious Disorders - Drug Targets
Title: Recent Advances in Prion Chemotherapeutics
Volume: 9 Issue: 1
Author(s): Valerie L. Sim and Byron Caughey
Affiliation:
Keywords: Prion, PrP, chemotherapeutic, decontamination, prophylaxis, polyanion, conversion
Abstract: The transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. Many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. However, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. There is increasing pressure to find effective decontaminants for blood supplies, as variant Creutzfeldt Jakob Disease (vCJD) has been shown to be transmissible by blood, and to find non-toxic preventative therapies, with ongoing cases of Bovine Spongiform Encephalopathy (BSE) and the spread of Chronic Wasting Disease (CWD). Within the realm of chemotherapeutic approaches, much research has focussed on blocking the conversion of the normal form of prion protein (PrPc) to its abnormal counterpart (PrPres). Structurally, these chemotherapeutic agents are often polyanionic or polycyclic and may directly bind PrPc or PrPres, or act by redistributing, sequestering, or downregulating PrPc, thus preventing its conversion. There are also some polycationic compounds which proport to enhance the clearance of PrPres. Other targets include accessory molecules such as the laminin receptor precursor which influences conversion, or cell signalling molecules which may be required for pathogenesis. Of recent interest are the possible neuroprotective effects of some drugs. Importantly, there is evidence that combining compounds may provide synergistic responses. This review provides an update on current testing methods, therapeutic targets, and promising candidates for chemical-based therapy.
Export Options
About this article
Cite this article as:
Sim L. Valerie and Caughey Byron, Recent Advances in Prion Chemotherapeutics, Infectious Disorders - Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/1871526510909010081
DOI https://dx.doi.org/10.2174/1871526510909010081 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Substrates and Inhibitors of Human Multidrug Resistance Associated Proteins and the Implications in Drug Development
Current Medicinal Chemistry The Role of Mitochondria in Brain Aging and the Effects of Melatonin
Current Neuropharmacology Platelets as Potential Link Between Diabetes and Alzheimer's Disease
Current Alzheimer Research Early Diagnosis of Alzheimers Disease: Is MCI Too Late?
Current Alzheimer Research Genetic Variations in CHRNA7 or CHRFAM7 and Susceptibility to Dementia
Current Drug Targets Pomegranate Extract Modulates Processing of Amyloid-β Precursor Protein in an Aged Alzheimer`s Disease Animal Model
Current Alzheimer Research Molecular Mechanisms of Ischemic Neuronal Cell Death - With Relevance to Alzheimers Disease
Current Alzheimer Research Disrupted White Matter Networks from Subjective Memory Impairment to Amnestic Mild Cognitive Impairment
Current Alzheimer Research Editorial: “Phytochemicals for Human Diseases: An Update”
Current Drug Targets Membrane Interacting Peptides: A Review
Current Protein & Peptide Science The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion
Current Alzheimer Research Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide
Current Medicinal Chemistry Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Current Alzheimer Research Neuroprotective Strategies for Parkinsons Disease
Current Neuropharmacology EDITORIAL [Hot Topic: Diabetes Cardiovascular Complications (Guest Editor: Costanza Emanueli)]
Endocrine, Metabolic & Immune Disorders - Drug Targets Isatin Hybrids and Their Pharmacological Investigations
Mini-Reviews in Medicinal Chemistry Perspectives on Medicinal Properties of Benzoquinone Compounds
Mini-Reviews in Medicinal Chemistry Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study
Current Alzheimer Research Neuronal and Vascular Oxidative Stress in Alzheimers Disease
Current Neuropharmacology Traumatic Brain Injury as a Risk Factor for Schizophrenia
Current Psychiatry Reviews