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The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy

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Abstract

Microtubule-associated protein tau (MAPT) is a gene responsible for encoding tau protein, which is tightly implicated in keeping the function of microtubules and axonal transport. Hyperphosphorylated tau protein participates in the formation of neurofibrillary tangles (NFTs), which characterize many neurodegenerative disorders termed tauopathies. Genome-wide association studies (GWAS) have demonstrated numerous single nucleotide polymorphisms (SNPs) located in MAPT associated with various neurodegenerative diseases. Thus, it has been presumed that MAPT plays a crucial role in pathogenesis of neurodegeneration via affecting the structure and function of tau. Here, we review the advanced studies to summarize the biochemical properties of MAPT and its encoded protein, as well as the genetics and epigenetics of MAPT in neurodegeneration. Finally, given the potential mechanisms of MAPT to neurodegeneration pathogenesis, targeting MAPT and tau might present significant treatments of MAPT mutation-related neurodegeneration. Affirmatively, the identification of MAPT is extremely beneficial for improving our understanding of the pathogenesis of various neurodegenerative diseases and developing the mechanism-based therapies.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81371406, 81171209, 81571245,81501103), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China

    Cheng-Cheng Zhang & Lan Tan

  2. Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, China

    Ang Xing

  3. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Meng-Shan Tan, Lan Tan & Jin-Tai Yu

  4. Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA

    Jin-Tai Yu

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  1. Cheng-Cheng Zhang
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  4. Lan Tan
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Correspondence to Lan Tan or Jin-Tai Yu.

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Zhang, CC., Xing, A., Tan, MS. et al. The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy. Mol Neurobiol 53, 4893–4904 (2016). https://doi.org/10.1007/s12035-015-9415-8

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