Prion diseases (PrD) are unique neurodegenerative conditions with sporadic, genetic, and infectious etiologies. The agent responsible for these pathologies is a misfolded conformation of the prion protein (PrP). Although a process of autocatalytic “conversion” is known to mediate disease transmission, important gaps still remain regarding the physiological function of PrP and its relevance to pathogenesis, the molecular and cellular mechanisms mediating neurotoxicity and transmission, and the PrP conformations responsible for neurotoxicity. New Drosophila models expressing mammalian PrP have revealed physiological insight into PrP function and opened the door to significant progress in prion transmission and PrP neurotoxicity. Importantly, flies expressing human PrP showing a robust eye phenotype will allow performing genetic screens to uncover novel mechanisms mediating PrP neurotoxicity.
Bibliographical noteFunding Information:
We want to thank the Bloomington Drosophila Stock Center (NIH P40OD018537) for Drosophila strains and Javier A. Fernandez-Ambite for assistance with the figures. This work was completed in part with the support of the NIH grant R21 NS096627-01A1 to PFF.
© 2017 Elsevier Ltd