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pubmed:abstractText |
To investigate the in vivo functions of normal prion protein (PrP) in Drosophila, we utilized characterized transgenic flies expressing ³(F)?-tagged mouse PrP (Mo-PrP³(F)?). The neurotoxicity of pathogenic Machado-Joseph Disease (MJD) glutamine (Q) 78 and 127Q proteins were enhanced by the co-expression of Mo-PrP³(F)?in the fly eyes, while the eyes of controls flies and flies expressing Mo-PrP³(F)?) alone or together with MJD-Q27 or 20Q proteins did not show any defect. Susceptibilities to H?O?, paraquat, and Dithiothreitol (DTT) were altered in Mo-PrP³(F)? flies. In addition, Mo-PrP³(F)? 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)? may enhance the neurotoxicity of pathogenic Poly-Q proteins by perturbing oxidative and autophagy signaling.
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