甲醛诱导Tau蛋白形成“孔道样”聚集结构

Pore-like Aggregates of Tau Protein Induced by Formaldehyde

尽管Lin等(University of California,Santa Barbara)就蛋白构象病中细胞死亡的机制提出了"非特异性淀粉样离子通道"(aspecific amyloid ion channels)学说,但到目前为止,尚未发现神经Tau蛋白能形成"孔道样"聚集结构,也未寻找到可以导致蛋白质形成"孔道样"聚集结构的诱导剂.依据本实验室提出的"散发性老年痴呆发生发展中的内源性甲醛慢性损伤"假说,采用一定浓度的甲醛与Tau蛋白进行温育,观察到甲醛可以明显诱导Tau蛋白分子聚集并形成淀粉样沉积物,同时也观察到了Tau蛋白"孔道样"聚集结构.上述结果为探索甲醛诱导Tau蛋白错误折叠形成的产物导致细胞代谢障碍和死亡的机制提供了新的研究思路.

Though the hypothesis of＂aspecific amyloid ion channels＂has been proposed by Lin,et al（University of California,Santa Barbara） to explain the mechanism of metabolic dysfunction and cell death during protein conformational diseases,the＂pore-like＂aggregates of misfolded neural Tau have not been observed.Revulsants involved in the formation of＂pore-like＂aggregates have not been found yet.According to the hypothesis＂chronic impairment resulted from abnormally-increased endogenous formaldehyde is one of the important risk factors related to sporadic senile dementia＂,formaldehyde has been utilized to incubate with Tau protein resulting in amyloid-like deposits with marked cytotoxicity.Under the experimental conditions,0.5%formaldehyde-treated Tau could form＂pore-like＂aggregates.These results may deliver a novel approach to study the mechanism of cellular metabolic disturbance,even cell death,which is induced by formaldehyde-treated neural Tau.