Overlapping the Tryptophan Catabolite (TRYCAT) and Melatoninergic Pathways in Alzheimer's Disease.
Study Goal
The researchers aimed to explore how interactions between the TRYCAT and melatoninergic pathways contribute to Alzheimer's disease (AD) pathology and treatment implications.
Results Summary
The study found that decreased melatonin synthesis due to TRYCAT pathway activation impacts AD progression by altering immune activity and trophic support, linking these pathways to AD's etiology and treatment.
Population
Alzheimer's disease patients, with a focus on those with associated depression.
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
oxidative and nitrosative stress and proinflammatory cytokine-driven indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) | increase | neuroregulatory TRYCATs, such as kynurenic acid and quinolinic acid | - | - | leads to the synthesis of | #1 |
neuroregulatory TRYCATs, such as kynurenic acid and quinolinic acid | neutral | neuronal functioning and survival | - | - | have significant impacts on | #2 |
neuroregulatory TRYCATs, such as kynurenic acid and quinolinic acid | neutral | Alzheimer's disease (AD) | - | - | contributing to the changes seen in | #3 |
IDO and TDO-driven TRYCATs | decrease | tryptophan for serotonin synthesis | - | - | decrease the availability of | #4 |
IDO and TDO-driven TRYCATs | decrease | serotonin for N-acetylserotonin (NAS) and melatonin synthesis | - | - | decrease the availability of | #5 |
loss of NAS and melatonin | neutral | the etiology, course and treatment of AD | - | - | has significant consequences for | #6 |
loss of NAS and melatonin | neutral | trophic support | - | - | changing the levels of | #7 |
loss of NAS and melatonin | neutral | immune activity | - | - | modulating the patterning of | #8 |
Activation of the trptophan catabolite (TRYCAT) pathways by oxidative and nitrosative stress and proinflammatory cytokine-driven indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) leads to the synthesis of a number of neuroregulatory TRYCATs, such as kynurenic acid and quinolinic acid. Such TRYCATs have significant impacts on neuronal functioning and survival contributing to the changes seen in Alzheimer's disease (AD), including in its association with depression as well as alterations in the reactivity of immune and glia cells. By decreasing the availability of tryptophan for serotonin synthesis, such IDO and TDO-driven TRYCATs, also decrease the availability of serotonin for N-acetylserotonin (NAS) and melatonin synthesis. The loss of NAS and melatonin has significant consequences for the etiology, course and treatment of AD, including via interactions with altered TRYCATs, but also by changing the levels of trophic support and modulating the patterning of immune activity. In this review, we look at how such interactions of the TRYCAT and melatoninergic pathways link a plethora of previously diffuse data in AD as well as the treatment implications and future research directions that such data would suggest.