Possible role for Ca2+ in the pathophysiology of the prion protein?
Possible role for Ca2+ in the pathophysiology of the prion protein?
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DOI：
10.1002/biof.161
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发表时间：
2011-05
期刊：
影响因子：
6
通讯作者：
C. Peggion;A. Bertoli;M. Sorgato
中科院分区：
文献类型：
--
作者：
C. Peggion;A. Bertoli;M. Sorgato
传染性海绵状脑病（Transmissible spongiform encephalopathy，又称朊病毒病）是由朊病毒（prion）引起的一种致死性神经退行性疾病，其主要成分是朊病毒蛋白PrP（C）的一种异常构象异构体。朊病毒相关神经变性的机制和PrP（C）的生理功能尚不清楚，尽管现在越来越多地认识到PrP（C）在细胞分化和存活中起作用。因此，PrP（C）表现出二分属性，因为它可以从正常条件下的良性功能转变为疾病期间神经元死亡的触发。通过回顾朊病毒感染模型和PrP敲除范式的数据，我们在这里讨论了Ca（2+）是PrP（C）多方面行为背后隐藏因素的可能性。通过在几乎所有的细胞信号传导过程中发挥作用，Ca（2+）可能解释PrP（C）病理生理学的各个方面，包括最近提出的PrP（C）在阿尔茨海默病中作为突触变性的介体。
Transmissible spongiform encephalopathies, or prion diseases, are lethal neurodegenerative disorders caused by the infectious agent named prion, whose main constituent is an aberrant conformational isoform of the cellular prion protein, PrP(C) . The mechanisms of prion-associated neurodegeneration and the physiologic function of PrP(C) are still unclear, although it is now increasingly acknowledged that PrP(C) plays a role in cell differentiation and survival. PrP(C) thus exhibits dichotomic attributes, as it can switch from a benign function under normal conditions to the triggering of neuronal death during disease. By reviewing data from models of prion infection and PrP-knockout paradigms, here we discuss the possibility that Ca(2+) is the hidden factor behind the multifaceted behavior of PrP(C) . By featuring in almost all processes of cell signaling, Ca(2+) might explain diverse aspects of PrP(C) pathophysiology, including the recently proposed one in which PrP(C) acts as a mediator of synaptic degeneration in Alzheimer's disease.