Targeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative Diseases.
Targeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative Diseases.
复制标题
DOI：
10.4172/2161-0460.1000443
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Zhou, Xiao Zhen
中科院分区：
文献类型：
--
作者：
Albayram, Onder;Angeli, Peter;Zhou, Xiao Zhen
Tau是一种微管相关蛋白，与神经退行性疾病（统称为Tau病）密切相关，包括阿尔茨海默病和慢性创伤性脑病。在Thr231位点的tau磷酸化允许磷酸化的tau （p-tau）异构化成不同的顺式和反式构象。顺式，而非反式，p-tau不仅在阿尔茨海默病和慢性创伤性脑病中可检测到，而且在创伤性脑损伤后也可检测到，这取决于人类和动物模型中损伤的严重程度和频率。顺式p-tau不仅具有神经毒性，而且以朊病毒样的方式从一个神经元扩散到另一个神经元，是神经变性的主要驱动因素，可被顺式p-tau抗体有效中和。这为了解疾病发展、开发早期生物标志物和有效治疗牛头病变提供了一个令人兴奋的新机会。
Tau is a microtubule-associated protein heavily implicated in neurodegenerative diseases collectively known as tauopathies, including Alzheimer's disease and chronic traumatic encephalopathy. Phosphorylation of tau at Thr231 allows for the isomerization of phosphorylated tau (p-tau) into distinct cis and trans conformations. Cis, but not trans, p-tau is detectable not only in Alzheimer's disease and chronic traumatic encephalopathy, but also right after traumatic brain injury depending on injury severity and frequency both in humans and animal models. Cis p-tau is not only neurotoxic but also spreads from a neuron to another in a prion-like fashion, functioning as a primary driver of neurodegeneration, which can be effectively neutralized by cis p-tau antibody. This represents an exciting new opportunity for understanding disease development and developing early biomarkers and effective therapies of tauopathies.