Summary of project PR002694
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002694. The data can be accessed directly via it's Project DOI: 10.21228/M8F26W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002694 |
| Project DOI: | doi: 10.21228/M8F26W |
| Project Title: | Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration |
| Project Summary: | In the brain, tryptophan byproducts are involved in the biosynthesis of proteins, energy-rich molecules (e.g., NAD+), and neurotransmitters (serotonin and melatonin). Impaired tryptophan catabolism, seen in aging, neurodegeneration and psychiatric diseases affects mood, learning, and sleep; however, the reasons for those impairments in elder and these ailments remain unknown. Our results from cellular, Drosophila melanogaster, and mouse models indicate that SIRT6 regulates tryptophan catabolism by balancing its usage. Mechanistically, SIRT6 regulates tryptophan and sleep quality through changes in gene expression of key genes (e.g., TDO2, AANAT), which results in elevated concentration of neurotoxic metabolites from the kynurenic pathway at the expense of serotonin and melatonin production. Such neurotoxic metabolites can affect various processes in the brain. However, by redirecting tryptophan through TDO2 inhibition in our new SIRT6-KO D. melanogaster model, the impairments in neuromotor behavior and vacuolar formation - parameters of neurodegeneration - could be significantly reversed. |
| Institute: | VIB-KU Leuven Center for Cancer Biology |
| Last Name: | Fernández-García |
| First Name: | Juan |
| Address: | Campus Gasthuisberg, O&N4, Herestraat 49, box 912, 3000 Leuven, Belgium |
| Email: | juan.fernandezgarcia@kuleuven.be |
| Phone: | +32 16 37 32 61 |
Summary of all studies in project PR002694
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004267 | Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration - Human cell lines | Homo sapiens | VIB-KU Leuven Center for Cancer Biology | MS | 2025-10-30 | 1 | 26 | Uploaded data (28.1G)* |
| ST004268 | Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration - Drosophila | Drosophila melanogaster | VIB-KU Leuven Center for Cancer Biology | MS | 2025-10-30 | 1 | 28 | Uploaded data (30.9G)* |
