title: Normal prion protein in Drosophila enhances the toxicity of pathogenic polyglutamine proteins and alters susceptibility to oxidative and autophagy signaling modulators.
abstract: To investigate the in vivo functions of normal prion protein (PrP) in Drosophila, we utilized characterized transgenic flies expressing ³(F)⁴-tagged mouse PrP (Mo-PrP³(F)⁴). The neurotoxicity of pathogenic Machado-Joseph Disease (MJD) glutamine (Q) 78 and 127Q proteins were enhanced by the co-expression of Mo-PrP³(F)⁴in the fly eyes, while the eyes of controls flies and flies expressing Mo-PrP³(F)⁴) alone or together with MJD-Q27 or 20Q proteins did not show any defect. Susceptibilities to H₂O₂, paraquat, and Dithiothreitol (DTT) were altered in Mo-PrP³(F)⁴ flies. In addition, Mo-PrP³(F)⁴ flies were significantly more susceptible to the perturbation of autophagy signaling by an autophagy inhibitor, 3-methyladenine (3-MA), and inducer, LiCl. Taken together, our data suggest that Mo-PrP³(F)⁴ may enhance the neurotoxicity of pathogenic Poly-Q proteins by perturbing oxidative and autophagy signaling.
authors.affiliation: ILSONG Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Republic of Korea.
authors.forename: Yunwoong
authors.initials: Y
authors.lastname: Park
authors.forename: Wontae
authors.initials: W
authors.lastname: Kim
authors.forename: A-Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jin Kyue
authors.initials: JK
authors.lastname: Choi
authors.forename: Namsin
authors.initials: N
authors.lastname: Park
authors.forename: Eui Kwan
authors.initials: EK
authors.lastname: Koh
authors.forename: Jongbok
authors.initials: J
authors.lastname: Seo
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Koh
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D004195:Disease Models, Animal; D004229:Dithiothreitol / Q000633:toxicity; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000196:embryology / Q000378:metabolism; D018021:Lithium Chloride / Q000633:toxicity; D017827:Machado-Joseph Disease / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008957:Models, Genetic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity; D010455:Peptides / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D056811:Unfolded Protein Response; D014867:Water / Q000494:pharmacology
chemical_list: D010455:Peptides; D011328:Prions; D014867:Water; C097188:polyglutamine; C025946:3-methyladenine; D018021:Lithium Chloride; D000225:Adenine; D010269:Paraquat; D004229:Dithiothreitol