Abstract
Prion diseases are fatal and incurable infectious neurodegenerative disorders affecting humans and other mammals. Prions are composed essentially if not solely of PrPSc, a misfolded form of the host-encoded PrP protein. PrPSc catalyzes the transconformation of the normal endogenous PrP (PrPC) into more PrPSc. Prion replication thus corresponds to the propagation of an altered folding state of PrP. Several prion proteins have also been identified in the simple model organism Saccharomyces cerevisiae. Yeast prion-based screening assays have allowed identification of drugs active against mammalian prions, thus revealing the existence of common prion propagation mechanisms conserved from yeast to human. To identify these conserved targets, antiprion compounds isolated in yeast can be used as baits in reverse screening strategies. Once identified, these targets could in turn lead to the development of mechanism-based cell-free antiprion screening assays. A reverse screening procedure has been performed for 6AP and GA, two antiprion compounds isolated using a yeast-based assay. Protein folding activity of the large ribosomal RNA was found to be a physical and a functional target of both 6AP and GA therefore suggesting that this activity of the ribosome may constitute a novel mechanism involved in prion propagation and, as a consequence, a new screening target.
Keywords: Mammalian Prion, Antiprion Drug Screening, Mouse Models, Saccharomyces cerevisiae, ribosomal RNA
Infectious Disorders - Drug Targets
Title: Procedure for Identification and Characterization of Drugs Efficient Against Mammalian Prion: From a Yeast-Based Antiprion Drug Screening Assay to In Vivo Mouse Models
Volume: 9 Issue: 1
Author(s): Cecile Voisset, Sven J. Saupe, Herve Galons and Marc Blondel
Affiliation:
Keywords: Mammalian Prion, Antiprion Drug Screening, Mouse Models, Saccharomyces cerevisiae, ribosomal RNA
Abstract: Prion diseases are fatal and incurable infectious neurodegenerative disorders affecting humans and other mammals. Prions are composed essentially if not solely of PrPSc, a misfolded form of the host-encoded PrP protein. PrPSc catalyzes the transconformation of the normal endogenous PrP (PrPC) into more PrPSc. Prion replication thus corresponds to the propagation of an altered folding state of PrP. Several prion proteins have also been identified in the simple model organism Saccharomyces cerevisiae. Yeast prion-based screening assays have allowed identification of drugs active against mammalian prions, thus revealing the existence of common prion propagation mechanisms conserved from yeast to human. To identify these conserved targets, antiprion compounds isolated in yeast can be used as baits in reverse screening strategies. Once identified, these targets could in turn lead to the development of mechanism-based cell-free antiprion screening assays. A reverse screening procedure has been performed for 6AP and GA, two antiprion compounds isolated using a yeast-based assay. Protein folding activity of the large ribosomal RNA was found to be a physical and a functional target of both 6AP and GA therefore suggesting that this activity of the ribosome may constitute a novel mechanism involved in prion propagation and, as a consequence, a new screening target.
Export Options
About this article
Cite this article as:
Voisset Cecile, Saupe J. Sven, Galons Herve and Blondel Marc, Procedure for Identification and Characterization of Drugs Efficient Against Mammalian Prion: From a Yeast-Based Antiprion Drug Screening Assay to In Vivo Mouse Models, Infectious Disorders - Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/1871526510909010031
DOI https://dx.doi.org/10.2174/1871526510909010031 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- Author Guidelines
- 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
-
Rational Basis for Nutraceuticals in the Treatment of Glaucoma
Current Neuropharmacology Editorial [Hot Topic: Novel Therapeutic Strategies in Neural Diseases Uncover Unexpected Disease Connections: From Neurodegeneration and Addiction to Pain and Depression (Guest Editor: Gonzalo Herradon)]
Current Pharmaceutical Design In silico Methods for Designing Antagonists to Anti-apoptotic Members of Bcl-2 Family Proteins
Mini-Reviews in Medicinal Chemistry The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer’s Disease
Current Pharmaceutical Design Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Regulatory Cascade of Neuronal Loss and Glucose Metabolism
CNS & Neurological Disorders - Drug Targets Mitochondria: A Promising Target for Anticancer Alkaloids
Current Topics in Medicinal Chemistry The Classic Basic Protein of Myelin – Conserved Structural Motifs and the Dynamic Molecular Barcode Involved in Membrane Adhesion and Protein-Protein Interactions
Current Protein & Peptide Science How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?
Current Women`s Health Reviews Editorial [Hot Topic: Amyloid-Associated Disease Mechanisms in Alzheimers Disease (Guest Editor: Jeroen J.M. Hoozemans)]
Current Drug Targets - CNS & Neurological Disorders Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives
CNS & Neurological Disorders - Drug Targets Exploration of Umbelliferone Based Derivatives as Potent MAO Inhibitors: Dry vs. Wet Lab Evaluation
Current Topics in Medicinal Chemistry Role of Forkhead Transcription Factors of the O Class (FoxO) in Development and Progression of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Integrated Analysis of Transcriptomic and Proteomic Data
Current Genomics The Emergence of Non-coding RNAs as Versatile and Efficient Therapeutic Tools
Current Gene Therapy The Emory Chemical Biology Discovery Center: Leveraging Academic Innovation to Advance Novel Targets through HTS and Beyond
Combinatorial Chemistry & High Throughput Screening Pathophysiology of Transmissible Spongiform Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Theoretical Approaches to Protein Aggregation
Protein & Peptide Letters Therapeutic Targets in Extracellular Protein Deposition Diseases
Current Medicinal Chemistry Polymeric Nanocarriers and Nanoreactors: A Survey of Possible Therapeutic Applications
Current Pharmaceutical Design