Summary of project PR001934
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 PR001934. The data can be accessed directly via it's Project DOI: 10.21228/M8QT5K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001934 |
| Project DOI: | doi: 10.21228/M8QT5K |
| Project Title: | Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes |
| Project Summary: | The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, although its potential role in disease pathogenesis is unknown. Here, we identified alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We found that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also found that one of the arginine-rich DPRs (PR) can directly contribute to glucose metabolism and metabolic stress. These findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model that opens several opportunities for therapeutic intervention. |
| Institute: | Thomas Jefferson University |
| Last Name: | Davide |
| First Name: | Trotti |
| Address: | 900 Walnut Street, Philadelphia, PA 19107, USA |
| Email: | davide.trotti@jefferson.edu |
| Phone: | 215-955-8416 |
Summary of all studies in project PR001934
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003112 | Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes | Mus musculus | Thomas Jefferson University | MS | 2024-03-29 | 1 | 20 | Uploaded data (349.9M)* |
| ST003118 | Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes - Study 2 | Mus musculus | Thomas Jefferson University | MS | 2024-03-29 | 1 | 10 | Uploaded data (284.5M)* |
