Summary of Study ST003118
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST003118 |
Study Title | Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes - Study 2 |
Study 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 | Trotti |
First Name | Davide |
Address | 900 Walnut Street, Philadelphia, PA 19107, USA |
davide.trotti@jefferson.edu | |
Phone | 215-955-8416 |
Submit Date | 2024-03-01 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2024-03-29 |
Release Version | 1 |
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Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | Sample source | Treatment |
---|---|---|---|
SA338035 | 2DG_1 | Brain | 2DG |
SA338036 | 2DG_5 | Brain | 2DG |
SA338037 | 2DG_4 | Brain | 2DG |
SA338038 | 2DG_2 | Brain | 2DG |
SA338039 | 2DG_3 | Brain | 2DG |
SA338040 | Saline_5 | Brain | Saline |
SA338041 | Saline_4 | Brain | Saline |
SA338042 | Saline_1 | Brain | Saline |
SA338043 | Saline_2 | Brain | Saline |
SA338044 | Saline_3 | Brain | Saline |
Showing results 1 to 10 of 10 |