Walker Lary C, Levine Harry, Mattson Mark P, Jucker Mathias
Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Trends Neurosci. 2006 Aug;29(8):438-43. doi: 10.1016/j.tins.2006.06.010. Epub 2006 Jun 27.
Numerous degenerative diseases are characterized by the aberrant polymerization and accumulation of specific proteins. These proteopathies include neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and the prion diseases, in addition to diverse systemic disorders, particularly the amyloidoses. The prion diseases have been shown to be transmissible by an alternative conformation of the normal cellular prion protein. Other proteopathies have been thought to be non-transmissible, but there is growing evidence that some systemic and cerebral amyloidoses can be induced by exposure of susceptible hosts to cognate molecular templates. As we review here, the mechanistic similarities among these diseases provide unprecedented opportunities for elucidating the induction of protein misfolding and assembly in vivo, and for developing an integrated therapeutic approach to degenerative proteopathies.
许多退行性疾病的特征是特定蛋白质的异常聚合和积累。这些蛋白质病包括神经疾病，如阿尔茨海默病、帕金森病、亨廷顿病和朊病毒病，此外还有各种全身性疾病，特别是淀粉样变性病。已证明朊病毒病可通过正常细胞朊蛋白的另一种构象进行传播。其他蛋白质病一直被认为是不可传播的，但越来越多的证据表明，一些全身性和脑淀粉样变性病可由易感宿主接触同源分子模板诱发。正如我们在此所综述的，这些疾病之间的机制相似性为阐明体内蛋白质错误折叠和组装的诱导过程，以及开发针对退行性蛋白质病的综合治疗方法提供了前所未有的机会。
