法国科学家日前发现,早老性痴呆症的致病蛋白质Tau虽然经常扮演神经细胞“杀手”的角色,但它在正常情况下却能对细胞的DNA(脱氧核糖核酸)进行保护。
这项研究由法国国家科研中心等机构共同完成。科学家在美国最新一期《生物化学杂志》上报告说,在患者脑中,已经发生变异的蛋白质Tau会大量吸附磷酸盐,然后聚集在神经细胞里,从而引发早老性痴呆症。
不过由吕克·比埃领导的研究小组日前发现,如果Tau一直处于正常状态,没有吸附过量的磷酸盐,那么它就会进入神经细胞的细胞核,对其中的DNA形成保护。科学家们利用实验鼠进行测试,结果证实,在缺乏正常Tau蛋白质的情况下,老鼠脑细胞中的DNA更易受到损害。
科学家表示,这一发现将帮助科学家进一步了解蛋白质Tau的特性,从而研究出针对早老性痴呆症的新疗法。
早老性痴呆症又名阿尔茨海默氏症,是最常见的老年痴呆症,临床症状表现为认知、记忆和语言功能障碍等。(生物谷Bioon.com)
生物谷推荐原文出处:
JBC doi: 10.1074/jbc.M110.199976
Nuclear tau: a key player in neuronal DNA protection
Audrey Sultan1, Fabrice Nesslany2, Marie Violet1, Severine Begard1, Anne Loyens1, Smail Talahari2, Zeyni Mansuroglu3, Daniel Marzin4, Nicolas Sergeant1, Sandrine Humez1, Morvane Colin1, Eliette Bonnefoy3, Luc Buee1 and Marie-Christine Galas1,*
Abstract
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease that is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the over-expression of hTau (human Tau) targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response.