From tau phosphorylation to tau aggregation: what about neuronal death?
From tau phosphorylation to tau aggregation: what about neuronal death?
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DOI：
10.1042/bst0380967
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发表时间：
2010-08-01
影响因子：
3.9
通讯作者：
Sergeant, Nicolas
中科院分区：
文献类型：
--
作者：
Buee, Luc;Troquier, Laetitia;Sergeant, Nicolas
Tau病理学的特征在于异常和过度磷酸化的Tau蛋白的细胞内聚集体。它在许多神经退行性疾病中遇到，但也在衰老中遇到。这些神经退行性疾病被称为tau蛋白病。tau聚集体的比较生物化学显示，它们在tau同种型磷酸化和含量方面都不同，这使得能够对tau蛋白病进行分子分类。在痴呆的情况下，NFD（神经元变性）严重程度与认知障碍相关，并且通常被认为是神经元死亡。使用tau动物模型，tau磷酸化、聚集和神经元死亡的动力学分析与电生理和行为参数平行，表明认知缺陷和神经元细胞死亡之间的脱节。Tau磷酸化和聚集是认知障碍的早期事件。在最老的年龄之前没有观察到神经元死亡。一系列事件可能是毒性磷酸化tau物质的形成、它们的聚集、神经元缠结的形成（从预缠结到鬼缠结）和最后的神经元细胞死亡。这个序列将持续15到25年，人们可以问毒性磷酸化tau物质的聚集是否是对细胞死亡的保护。细胞凋亡需要24小时，但NFD持续24年，最终杀死神经元，或者更确切地说，保护它超过20年。总之，这些数据表明，NFD是神经元死亡前的一种短暂状态，在该阶段可能进行治疗干预。
Tau pathology is characterized by intracellular aggregates of abnormally and hyperphosphorylated tau proteins. It is encountered in many neurodegenerative disorders, but also in aging. These neurodegenerative disorders are referred to as tauopathies. Comparative biochemistry of the tau aggregates shows that they differ in both tau isoform phosphorylation and content, which enables a molecular classification of tauopathies. In conditions of dementia, NFD (neurofibrillary degeneration) severity is correlated to cognitive impairment and is often considered as neuronal death. Using tau animal models, analysis of the kinetics of tau phosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a disconnection between cognition deficits and neuronal cell death. Tau phosphorylation and aggregation are early events followed by cognitive impairment. Neuronal death is not observed before the oldest ages. A sequence of events may be the formation of toxic phosphorylated tau species, their aggregation, the formation of neurofibrillary tangles (from pre-tangles to ghost tangles) and finally neuronal cell death. This sequence will last from 15 to 25 years and one can ask whether the aggregation of toxic phosphorylated tau species is a protection against cell death. Apoptosis takes 24 h, but NFD lasts for 24 years to finally kill the neuron or rather to protect it for more than 20 years. Altogether, these data suggest that NFD is a transient state before neuronal death and that therapeutic interventions are possible at that stage.