The Accumulation of Tau in Postsynaptic Structures: A Common Feature in Multiple Neurodegenerative Diseases?

The Accumulation of Tau in Postsynaptic Structures: A Common Feature in Multiple Neurodegenerative Diseases?
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DOI:
10.1177/1073858420916696
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发表时间:
2020-10
期刊:
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子:
--
通讯作者:
Liao D
Liao D
中科院分区:
其他
文献类型:
--
作者:
Teravskis PJ;Ashe KH;Liao D

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越来越多的研究表明,神经退行性疾病和痴呆不是由独特的、孤立的细胞机制引起的,而是由多种促进机制引起的,表现为不同的临床表现。然而,不同的神经退行性疾病也有共同的病理特征和细胞机制。其中一种机制涉及到微管相关蛋白tau从轴突重新分布到神经元的体树突隔室,随后tau错误定位到树突棘,导致突触后功能缺陷。在这里,我们回顾了触发tau重新分配到细胞体和树突树的各种信号通路,以及它在树突棘的错误定位。不同疾病模型中的多种途径趋同于这一最终的共同途径,表明它可能是开发神经退行性疾病新疗法的一个有吸引力的靶点。
Increasingly, research suggests that neurodegenerative diseases and dementias are caused not by unique, solitary cellular mechanisms, but by multiple contributory mechanisms manifesting as heterogeneous clinical presentations. However, diverse neurodegenerative diseases also share common pathological hallmarks and cellular mechanisms. One such mechanism involves the redistribution of the microtubule associated protein tau from the axon into the somatodendritic compartments of neurons, followed by the mislocalization of tau into dendritic spines, resulting in postsynaptic functional deficits. Here we review various signaling pathways that trigger the redistribution of tau to the cell body and dendritic tree, and its mislocalization to dendritic spines. The convergence of multiple pathways in different disease models onto this final common pathway suggests that it may be an attractive pathway to target for developing new treatments for neurodegenerative diseases.
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