TDO as a therapeutic target in brain diseases

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• 作者：Cheng-Peng Yu ; Ze-Zheng Pan ; Da-Ya Luo
• 刊名：Metabolic Brain Disease
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：31
• 期：4
• 页码：737-747
• 全文大小：696 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Neurology
  Biochemistry
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7365
• 卷排序：31

文摘

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.KeywordsTDOTryptophan metabolismSchizophreniaAlzheimer’s diseaseGlioma