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Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease

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Summary

As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease (AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) are the most implicated. Accumulation of the hyperphosphorylated tau induces synaptic toxicity and cognitive impairments. Here, we review the upstream factors or pathways that can regulate GSK-3β or PP2A activity mainly based on our recent findings. We will also discuss the mechanisms that may underlie tau-induced synaptic toxicity.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Rong-hong Ma  (马荣红)

  2. Department of Endocrinology, Liyuan Hospital, Key Laboratory of Hubei Province for Neurological Disorders, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yao Zhang  (张 瑶)

  3. Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Hubei Province and Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xiao-yue Hong  (洪小月), Jun-fei Zhang  (张俊菲), Jian-Zhi Wang  (王建枝) & Gong-ping Liu  (刘恭平)

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  1. Rong-hong Ma  (马荣红)
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Correspondence to Jian-Zhi Wang  (王建枝) or Gong-ping Liu  (刘恭平).

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Ma, Rh., Zhang, Y., Hong, Xy. et al. Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 37, 307–312 (2017). https://doi.org/10.1007/s11596-017-1732-x

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  • DOI: https://doi.org/10.1007/s11596-017-1732-x

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