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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
  • 192 Downloads

Abstract

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.

Keywords

IDO TDO Kynurenine pathway Depression IDO inhibitors TDO inhibitors 

Abbreviations

IDO

indoleamine 2,3-dioxygenase

TDO

tryptophan 2,3-dioxygenase

KATs

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

KMO

kynurenine 3-monooxygenase

KYNU

kynureninase

3-HAO

3-hydroxyanthranilic acid 3,4-dioxygenase

ACMSD

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

QPRT

quinolinate phosphoribosyl-transferase

KYNU

kynureninase

NAD

Nicotinamide adenine dinucleotide

TPH

tryptophan hydroxylase

AADC

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

AA-NAT

serotonin N-acetyltransferase

HIOMT

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

BBB

blood brain barrier

HPA axis

hypothalamic-pituitary-adrenal axis

LNAA

large neutral amino acid

TNF

tumor necrosis factor

LAT-1

L-type amino acid transporter 1

Notes

Acknowledgments

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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