Unterberger Ursula, Voigtländer Till, Budka Herbert
Institute of Neurology, Medical University of Vienna, AKH, Austria.
Acta Neuropathol. 2005 Jan;109(1):32-48. doi: 10.1007/s00401-004-0953-9. Epub 2005 Jan 12.
Prion diseases are rare neurological disorders that may be of genetic or infectious origin, but most frequently occur sporadically in humans. Their outcome is invariably fatal. As the responsible pathogen, prions have been implicated. Prions are considered to be infectious particles that represent mainly, if not solely, an abnormal, protease-resistant isoform of a cellular protein, the prion protein or PrP(C). As in other neurodegenerative diseases, aggregates of misfolded protein conformers are deposited in the CNS of affected individuals. Pathogenesis of prion diseases comprises mainly two equally important, albeit essentially distinct, topics: first, the mode, spread, and amplification of infectivity in acquired disease, designated as peripheral pathogenesis. In this field, significant advances have implicated an essential role of lymphoid tissues for peripheral prion replication, before a likely neural spread to the CNS. The second is the central pathogenesis, dealing, in addition to spread and replication of prions within the CNS, with the mechanisms of nerve cell damage and death. Although important roles for microglial neurotoxicity, oxidative stress, and complement activation have been identified, we are far from complete understanding, and therapeutic applications in prion diseases still need to be developed.
朊病毒病是罕见的神经疾病，其病因可能是遗传或感染，但在人类中最常见的是散发性的。其结果必然是致命的。作为致病病原体，朊病毒已被牵连其中。朊病毒被认为是感染性颗粒，主要（如果不是唯一的话）代表细胞蛋白朊病毒蛋白或PrP(C)的一种异常的、抗蛋白酶的异构体。与其他神经退行性疾病一样，错误折叠的蛋白质构象体聚集体沉积在受影响个体的中枢神经系统中。朊病毒病的发病机制主要包括两个同样重要但本质上不同的主题：第一，在获得性疾病中感染性的传播方式、扩散和扩增，称为外周发病机制。在这个领域，重大进展表明淋巴组织在外周朊病毒复制中起着重要作用，之后才可能向中枢神经系统进行神经扩散。第二个是中枢发病机制，除了朊病毒在中枢神经系统内的扩散和复制外，还涉及神经细胞损伤和死亡的机制。尽管已经确定了小胶质细胞神经毒性、氧化应激和补体激活的重要作用，但我们还远未完全了解，朊病毒病的治疗应用仍有待开发。
