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TYROBP in Alzheimer’s Disease

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Abstract

Recently, studies have provided convincing data that TYRO protein tyrosine kinase-binding protein (TYROBP), a key regulator in immune systems, is significantly upregulated in the brain of patients with Alzheimer’s disease (AD). TYROBP acts as a signaling adaptor protein for numerous cell surface receptors, playing important roles in signal transduction in dendritic cells, osteoclasts, macrophages, and microglia. Although several TYROBP-related cell surface receptors including triggering receptor expressed on myeloid 2 (TREM2), signal regulatory protein β1 (SIRPβ1), and complement receptor 3 (CR3) were found to participate in the pathogenesis of AD, the role of TYROBP in AD still remains elusive. Emerging piece of evidence has demonstrated that TYROBP could enhance phagocytic activity of microglia, which is responsible for the clearance of amyloid-β (Aβ) peptides and apoptotic neurons. TYROBP also participates in suppression of inflammatory responses by repression of microglia-mediated cytokine production and secretion. In this article, we introduce the structure, localization, and function of TYROBP. Meanwhile, we review recent articles concerning the association of TYROBP and its related receptors with AD pathogenesis and speculate the possible roles of TYROBP in this disease. Based on the potential protective actions of TYROBP in AD pathogenesis, targeting TYROBP might provide new opportunities for AD treatment.

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Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China to L.T. (81171209, 81371406) and J.T.Y. (81000544), the grants from the Shandong Provincial Natural Science Foundation to L.T. (ZR2011HZ001) and J.T.Y. (ZR2010HQ004), the Medicine and Health Science Technology Development Project of Shandong Province to L.T. (2011WSA02018) and J.T.Y. (2011WSA02020), and the Innovation Project for Postgraduates of Jiangsu Province to T.J. (CXLX13_561).

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

    Jing Ma, Lan Tan & Jin-Tai Yu

  2. Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, Shandong, China

    Teng Jiang, Lan Tan & Jin-Tai Yu

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  1. Jing Ma
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  2. Teng Jiang
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  3. Lan Tan
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Correspondence to Lan Tan or Jin-Tai Yu.

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Jing Ma and Teng Jiang contributed equally to this work.

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Ma, J., Jiang, T., Tan, L. et al. TYROBP in Alzheimer’s Disease. Mol Neurobiol 51, 820–826 (2015). https://doi.org/10.1007/s12035-014-8811-9

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