Metabolic Brain Disease

, Volume 33, Issue 6, pp 1787–1800 | Cite as

IDO and TDO as a potential therapeutic target in different types of depression

  • Yanjie Qin
  • Nanxi Wang
  • Xinlin Zhang
  • Xuemei Han
  • Xuejia Zhai
  • Yongning Lu
Review Article


Depression is highly prevalent worldwide and a leading cause of disabilty. However, the medications currently available to treat depression fail to adequately relieve depressive symptoms for a large number of patients. Research into the aberrant overactivation of the kynurenine pathway and the production of various active metabolites has brought new insight into the progression of depression. IDO and TDO are the first and rate-limiting enzymes in the kynurenine pathway and regulate the production of active metabolites. There is substantial evidence that TDO and IDO enzyme are activated during depression, and therefore, IDO and TDO inhibitors have been identified as ideal therapeutic targets for depressive disorder. Hence, this review will focus on the kynurenine branch of tryptophan metabolism and describe the role of IDO and TDO in the pathology of depression. In addition, this review will compare the relative imbalance between KYNA and neurotoxic kynurenine metabolites in different psychiatric disorders. Finally, this review is also directed toward assessing whether IDO and TDO are potential therapeutic target in depression associated with other diseases such as diabetes and/or cancer, as well as the development of potent IDO and TDO inhibitors.


IDO TDO Kynurenine pathway Depression IDO inhibitors TDO inhibitors 



indoleamine 2,3-dioxygenase


tryptophan 2,3-dioxygenase


(KAT I, KAT II, KAT III), kynurenine amino transferase 1, 2 and 3


kynurenine 3-monooxygenase




3-hydroxyanthranilic acid 3,4-dioxygenase


α-amino-β- carboxymuconic-epsilon-semialdehyde decarboxylase


quinolinate phosphoribosyl-transferase




Nicotinamide adenine dinucleotide


tryptophan hydroxylase


(Aromatic-L-amino acid decarboxylase; also known as dopa decarboxylase; DDC)


serotonin N-acetyltransferase


5-hydroxyindole-O-methyltransferase [also known as Acetylserotonin O-methyltransferase (ASMT)]


blood brain barrier

HPA axis

hypothalamic-pituitary-adrenal axis


large neutral amino acid


tumor necrosis factor


L-type amino acid transporter 1



This review was supported by a grant from the National Natural Science Foundation of China (Nos. 81473287 and 81673715)

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Authors and Affiliations

  1. 1.Department of Pharmacy, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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