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Prion disease modelled in Drosophila

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Smith, Andrew 
Fleck, Oliver 
Spiropoulos, John 
Andréoletti, Olivier 

Abstract

Prion diseases are fatal neurodegenerative conditions of humans and various vertebrate species that are transmissible between individuals of the same or different species. A novel infectious moiety referred to as a prion is considered responsible for transmission of these conditions. Prion replication is believed to be the cause of the neurotoxicity that arises during prion disease pathogenesis. The prion hypothesis predicts that the transmissible prion agent consists of PrPSc, which is comprised of aggregated misfolded conformers of the normal host protein PrPC. It is important to understand the biology of transmissible prions and to identify genetic modifiers of prion-induced neurotoxicity. This information will underpin the development of therapeutic and control strategies for human and animal prion diseases. The most reliable method to detect prion infectivity is by in vivo transmission in a suitable experimental host, which to date have been mammalian species. Current prion bioassays are slow, cumbersome and relatively insensitive to low titres of prion infectivity, and do not lend themselves to rapid genetic analysis of prion disease. Here, we provide an overview of our novel studies that have led to the establishment of Drosophila melanogaster, a genetically well-defined invertebrate host, as a sensitive, versatile and economically viable animal model for the detection of mammalian prion infectivity and genetic modifiers of prion-induced toxicity.

Description

Acknowledgements: We thank our former PhD students who contributed towards the development of this Drosophila model. We acknowledge the Fly Facility, Department of Genetics, University of Cambridge.


Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research; doi: http://dx.doi.org/10.13039/501100000849


Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268

Keywords

Review, Drosophila, Infectivity, Neurodegeneration, Prion, Transmissible

Journal Title

Cell and Tissue Research

Conference Name

Journal ISSN

0302-766X
1432-0878

Volume Title

392

Publisher

Springer Berlin Heidelberg