More than thirty years have passed since the discovery of the prion protein
(PrP) and its causative role in transmissible spongiform encephalopathy. Since a
combination of both gain- and loss-of-function mechanisms may underlay prion
pathogenesis, understanding the physiological role of PrP may give important clues
about disease mechanisms. Historically, the primary strategy for prion research has
involved the use of human tissue, cell cultures and mammalian animal models.
Nevertheless, experimental difficulties of in vivo studies and controversial observations
obtained in these systems have stimulated the search for alternative animal models.
PrPC is highly conserved in mammals, and PrPC-related orthologs are expressed in
zebrafish, a vertebrate model organism suitable to study the mechanisms associated
with human diseases. Invertebrate models, as they do not express PrPC have served to
investigate the neurotoxic mechanisms of mammalian PrP. Here we overview most
recent advances in the study of PrP function in normal and pathogenic conditions based
on non-mammalian studies, highlighting the contribution of zebrafish, fly and worms to
our current understanding of PrP biology.
Keywords: Prion-related disorders, PrPC, physiology, neurotoxicity, mammals, zebrafish, Drosophila melanogaster,
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