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Approaches for discovering anti-prion compounds: lessons learned and challenges ahead
Maria Laura Bolognesi1, Giuseppe Legname
1Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna , Via Belmeloro 6, 40126 Bologna , Italy marialaura.bolognesi@unibo.it.
Expert Opinion on Drug Discovery
|February 17, 2015
Summary
Phenotypic screening offers a promising avenue for prion disease drug discovery by utilizing cell models to identify effective compounds. This approach, particularly drug repositioning, can accelerate the development of treatments for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Prion diseases share molecular underpinnings with other neurodegenerative conditions like Alzheimer's disease.
- Protein misfolding is a key mechanism in prion pathogenesis, offering therapeutic targets.
- Prion diseases serve as a model for neurodegenerative disorders, aiding drug development.
Purpose of the Study:
- To review phenotypic screening strategies for prion disease drug discovery.
- To explore the benefits of drug repositioning for developing prion disease therapeutics.
- To highlight the potential of combining safe, known molecules with phenotypic screening.
Main Methods:
- Discussion of phenotypic screening approaches.
- Analysis of drug repositioning as a strategy.
- Review of existing research on prion disease drug candidates.
- Utilizing scrapie-infected murine neuroblastoma cells for compound identification.
Main Results:
- Phenotypic screening, especially drug repositioning, shows high potential for prion disease drug discovery.
- Compounds like quinacrine, astemizole, guanabenz, and doxycycline have been identified using this approach.
- The use of cell-based assays provides a clear readout for drug efficacy.
Conclusions:
- Murine cell models have been instrumental in identifying prion-inhibiting compounds.
- Developing a human neuronal model is crucial for advancing drug discovery for human prion diseases.
- Further research into human-specific models is essential for effective prion disease therapeutics.

