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TDO as a therapeutic target in brain diseases

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Abstract

Tryptophan-2, 3-dioxygenase (TDO) is a heme-containing protein catalyzing the first reaction in the kynurenine pathway, which incorporates oxygen into the indole moiety of tryptophan and catalyzes it into kynurenine (KYN). The activation of TDO results in the depletion of tryptophan and the accumulation of kynurenine and its metabolites. These metabolites can affect the function of neurons and inhibit the proliferation of T cells. Increasing evidence demonstrates that TDO is a potential therapeutic target in the treatment of brain diseases as well as in the antitumor and transplant fields. Despite its growing popularity, there are few reviews only focusing on TDO. Hence, we herein review TDO by providing a comprehensive overview of TDO, including its biological functions as well as the evolution, structure and catalytic process of TDO. Additionally, this review will focus on the role of TDO in the pathology of three groups of brain diseases: Schizophrenia, Alzheimer’s disease (AD) and Glioma. Finally, we will also provide an opinion regarding the future developmental directions of TDO in brain diseases, especially whether TDO has a potential role in other brain diseases as well as the development and applications of TDO inhibitors as treatments.

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Acknowledgments

We thank the participants in this study. This work was supported by grants from the National Natural Science Foundation of China (Grant No.81160248 and 81560464 to DYL), the Natural Science Foundation of JiangXi Province (Grant No. 20142BAB205069 to ZZP) and the Department of Public Health of JiangXi Province (Grant No.20121156 to ZZP).

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Authors and Affiliations

  1. The Second Clinic Medical College, School of Medicine, Nanchang University, Nanchang, China

    Cheng-Peng Yu

  2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, China

    Ze-Zheng Pan & Da-Ya Luo

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  1. Cheng-Peng Yu
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  2. Ze-Zheng Pan
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Correspondence to Da-Ya Luo.

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Cheng-Peng Yu and Ze-Zheng Pan contributed equally to this work

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Yu, CP., Pan, ZZ. & Luo, DY. TDO as a therapeutic target in brain diseases. Metab Brain Dis 31, 737–747 (2016). https://doi.org/10.1007/s11011-016-9824-z

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