Prusiner S B, DeArmond S J
Department of Neurology, University of California, San Francisco 94143.
Brain Pathol. 1991 Jul;1(4):297-310. doi: 10.1111/j.1750-3639.1991.tb00673.x.
Scrapie and bovine spongiform encephalopathy of animals and Creutzfeldt-Jakob and Gerstmann-Sträussler-Scheinker diseases of humans are transmissible and genetic neurodegenerative diseases caused by prions. Infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein which is encoded by a chromosomal gene. An as yet unidentified post-translational process converts the cellular prion protein into an abnormal isoform. Scrapie neuropathology, incubation times, and prion synthesis in transgenic mice are controlled by the prion protein gene. Point mutations in the prion protein genes of animals and humans are genetically linked to development of neurodegeneration. Transgenic mice expressing mutant prion proteins spontaneously develop neurologic dysfunction and spongiform neuropathology. Studies of prion diseases may advance investigations of other neurodegenerative disorders and of how neurons differentiate, function for decades and grow senescent.
动物的羊瘙痒症和牛海绵状脑病，以及人类的克雅氏病和格斯特曼-施特劳斯勒-谢inker病，是由朊病毒引起的可传播的遗传性神经退行性疾病。传染性朊病毒颗粒如果不是完全由朊病毒蛋白的异常异构体组成，也主要由其组成，该蛋白由染色体基因编码。一个尚未确定的翻译后过程将细胞朊病毒蛋白转化为异常异构体。转基因小鼠的羊瘙痒症神经病理学、潜伏期和朊病毒合成由朊病毒蛋白基因控制。动物和人类朊病毒蛋白基因中的点突变与神经退行性变的发展存在遗传联系。表达突变朊病毒蛋白的转基因小鼠会自发出现神经功能障碍和海绵状神经病理学变化。对朊病毒疾病的研究可能会推动对其他神经退行性疾病以及神经元如何分化、数十年发挥功能并衰老的研究。
