朊病毒病的果蝇模型：对朊病毒蛋白功能、传播及神经毒性的深入了解
Drosophila models of prionopathies: insight into prion protein function, transmission, and neurotoxicity.
作者信息
Fernandez-Funez Pedro, Sanchez-Garcia Jonatan, Rincon-Limas Diego E
机构信息
Department of Biomedical Sciences, University of Minnesota Medical School, Duluth Campus, Duluth, MN 55811, USA.
Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
出版信息
Curr Opin Genet Dev. 2017 Jun;44:141-148. doi: 10.1016/j.gde.2017.03.013. Epub 2017 Apr 14.
Abstract
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.
摘要
朊病毒病（PrD）是一类独特的神经退行性疾病，具有散发性、遗传性和传染性病因。导致这些病变的病原体是朊病毒蛋白（PrP）的错误折叠构象。尽管已知一种自催化“转化”过程介导疾病传播，但在PrP的生理功能及其与发病机制的相关性、介导神经毒性和传播的分子及细胞机制，以及负责神经毒性的PrP构象方面，仍存在重大空白。表达哺乳动物PrP的新型果蝇模型揭示了对PrP功能的生理洞察，并为朊病毒传播和PrP神经毒性方面的重大进展打开了大门。重要的是，表达人类PrP并表现出强烈眼部表型的果蝇将有助于进行遗传筛选，以揭示介导PrP神经毒性的新机制。
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