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Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR-132/MeCP2 pathway.


ABSTRACT: Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Our results provide evidence for a novel role of tau in the regulation of presynaptic function.

SUBMITTER: Xie AJ 

PROVIDER: S-EPMC6516177 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR-132/MeCP2 pathway.

Xie Ao-Ji AJ   Hou Tong-Yao TY   Xiong Wan W   Huang He-Zhou HZ   Zheng Jie J   Li Ke K   Man Heng-Ye HY   Hu Ya-Zhuo YZ   Han Zhi-Tao ZT   Zhang Hong-Hong HH   Wei Na N   Wang Jian-Zhi JZ   Liu Dan D   Lu Youming Y   Zhu Ling-Qiang LQ  

Aging cell 20190227 3


Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detect  ...[more]

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