Aguzzi A, Heppner F L
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse. 12, University Hospital Zurich, CH-8091 Zurich, Switzerland.
Cell Death Differ. 2000 Oct;7(10):889-902. doi: 10.1038/sj.cdd.4400737.
Almost 20 years have passed since Stanley Prusiner proposed that the agent causing transmissible spongiform encephalopathies consists exclusively of a protein and termed it prion. A mixed balance can be drawn from the enormous research efforts that have gone into prion research during this time. On the negative side, the protein-only hypothesis has not been conclusively proven yet. On the positive side, our understanding of spongiform encephalopathies has experienced tremendous advances, mostly through human genetics, mouse transgenetics, and biophysical methods. Perhaps the most astonishing development is the realization that many human neurodegenerative diseases for which transmissibility has been more or less stringently excluded, may follow pathogenetic principles similar to those of prion diseases. Also, the hypothesis that prion-like phenomena may underlie certain non-genetic traits observed in yeast has resulted in the surprising recognition that the instructional self-propagating changes in protein conformation may be much more prevalent in nature than previously thought. The latter developments have been astonishingly successful, and one could now argue that the prion principle is much more solidly established in yeast than in mammals.
自从斯坦利·普鲁辛纳提出导致传染性海绵状脑病的病原体仅由一种蛋白质组成并将其命名为朊病毒以来，近20年过去了。在此期间，人们对朊病毒进行了大量研究，由此可以得出一个好坏参半的结论。从消极方面来看，仅蛋白质假说尚未得到最终证实。从积极方面来看，我们对海绵状脑病的理解取得了巨大进展，这主要得益于人类遗传学、小鼠转基因技术和生物物理方法。也许最令人惊讶的进展是，人们意识到许多曾或多或少被严格排除具有传染性的人类神经退行性疾病，可能遵循与朊病毒疾病相似的致病原理。此外，关于酵母中观察到的某些非遗传性状可能由类朊病毒现象引起的假说，令人惊讶地认识到蛋白质构象中指导性的自我传播变化在自然界中可能比以前认为得更为普遍。后一种进展非常成功，现在人们可以说，朊病毒原理在酵母中比在哺乳动物中确立得更为坚实。
