title: Prion Function and Pathophysiology in Non-Mammalian Models.
abstract: 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.
authors.affiliation: Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, PO Box 70031, Santiago. Chile.
authors.forename: N
authors.initials: N
authors.lastname: Guerrero
authors.affiliation: Biomedical Neuroscience Institute, Independencia 1027, Santiago. Chile.
authors.forename: M M
authors.initials: MM
authors.lastname: Meynard
authors.affiliation: Center for Geroscience, Brain Health and Metabolism, Santiago. Chile.
authors.forename: J
authors.initials: J
authors.lastname: Borgonovo
authors.affiliation: Center for Geroscience, Brain Health and Metabolism, Santiago. Chile.
authors.forename: K
authors.initials: K
authors.lastname: Palma
authors.affiliation: Institute of Biomedical Sciences (Sector A, Second Floor), Universidad de Chile, Independencia 1027, Santiago, P.O. Box 70031. Chile.
authors.forename: M L
authors.initials: ML
authors.lastname: Concha
authors.affiliation: Institute of Biomedical Sciences (Sector A, Second Floor), Universidad de Chile, Independencia 1027, Santiago, P.O. Box 70031. Chile.
authors.forename: C
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D004195:Disease Models, Animal; D004330:Drosophila; D006801:Humans; D017096:Prion Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015027:Zebrafish
chemical_list: D011328:Prions
keywords: Caenorhabditis elegans; Drosophila melanogaster; PrPC; Prion-related disorders; mammals; neurotoxicity; physiology; zebrafish