Tatzelt Jörg, Schätzl Hermann M
Department of Biochemistry, Neurobiochemistry, Ludwig-Maximilians-University Munich, Germany.
FEBS J. 2007 Feb;274(3):606-11. doi: 10.1111/j.1742-4658.2007.05633.x.
The biochemical nature and the replication of infectious prions have been intensively studied in recent years. Much less is known about the cellular events underlying neuronal dysfunction and cell death. As the cellular function of the normal cellular isoform of prion protein is not exactly known, the impact of gain of toxic function or loss of function, or a combination of both, in prion pathology is still controversial. There is increasing evidence that the normal cellular isoform of the prion protein is a key mediator in prion pathology. Transgenic models were instrumental in dissecting propagation of prions, disease-associated isoforms of prion protein and amyloid production, and induction of neurodegeneration. Four experimental avenues will be discussed here which address scenarios of inappropriate trafficking, folding, or targeting of the prion protein.
近年来，传染性朊病毒的生化性质及其复制已得到深入研究。而对于神经元功能障碍和细胞死亡背后的细胞事件，人们了解得要少得多。由于朊病毒蛋白正常细胞异构体的细胞功能尚不完全清楚，因此在朊病毒病理学中，毒性功能获得或功能丧失，或两者兼而有之的影响仍存在争议。越来越多的证据表明，朊病毒蛋白的正常细胞异构体是朊病毒病理学中的关键介质。转基因模型有助于剖析朊病毒的传播、朊病毒蛋白的疾病相关异构体和淀粉样蛋白的产生，以及神经退行性变的诱导。本文将讨论四条实验途径，它们涉及朊病毒蛋白运输不当、折叠错误或靶向错误的情况。
