Skip to content
2000
Volume 14, Issue 5
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

This mini-review focuses on the studies of late Prof. IP Lapin (1903 – 2012) and his research team on the role of methoxyindole and kynurenine (KYN) pathways of tryptophan (TRP) metabolism in the pathogenesis of depression and action mechanisms of antidepressant effect. In the late 60s of the last century Prof. IP Lapin suggested that “intensification of central serotoninergic processes is a determinant of the thymoleptic (mood elevating) component” while “activation of noradrenergic processes is responsible for psychoenergetic and motor-stimulating component of the clinical antidepressant effect”. The cause of serotonin deficiency in depression was attributed to the shunt of TRP “metabolism away from serotonin production towards KYN production” due to cortisol-induced activation of liver enzyme, tryptophan 2,3- dioxygenase, the rate-limiting enzyme of TRP – KYN pathway. Prof. Lapin suggested and discovered that KYN and its metabolites affect brain functions, and proposed the role of neurokynurenines in pathogenesis of depression and action mechanisms of antidepressant effect (kynurenine hypothesis). Further research suggested the antidepressant and cognition- enhancing effects of post-serotonin metabolite, N-acetylserotonin (NAS), an agonist to tyrosine kinase B (TrkB) receptor; and link between depression and chronic inflammation-associated disorders (e.g., insulin resistance, hepatitis C virus) via inflammation-induced activation of indoleamine 2,3– dioxygenase, brain located rate-limiting enzyme of TRY – KYN metabolism. NAS and kynurenines might be the targets for prevention and treatment of depression and associated conditions.

Loading

Article metrics loading...

/content/journals/cdt/10.2174/1389450111314050002
2013-05-01
2025-05-22
Loading full text...

Full text loading...

/content/journals/cdt/10.2174/1389450111314050002
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test