Summary of Study ST003112
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 | ST003112 |
Study Title | Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes |
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 | 2024-02-29 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzXML |
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 | Genotype | Treatment |
---|---|---|---|---|
SA338015 | C92DG_56 | Brain | C9orf72 | 2DG |
SA338016 | C92DG_07 | Brain | C9orf72 | 2DG |
SA338017 | C92DG_45 | Brain | C9orf72 | 2DG |
SA338018 | C92DG_47 | Brain | C9orf72 | 2DG |
SA338019 | C92DG_26 | Brain | C9orf72 | 2DG |
SA338020 | C92DG_30 | Brain | C9orf72 | 2DG |
SA338021 | C92DG_34 | Brain | C9orf72 | 2DG |
SA338022 | C9S_57 | Brain | C9orf72 | Saline |
SA338023 | C9S_69 | Brain | C9orf72 | Saline |
SA338024 | C9S_50 | Brain | C9orf72 | Saline |
SA338025 | C9S_43 | Brain | C9orf72 | Saline |
SA338026 | C9S_33 | Brain | C9orf72 | Saline |
SA338027 | C9S_11 | Brain | C9orf72 | Saline |
SA338028 | C9S_29 | Brain | C9orf72 | Saline |
SA338029 | WTS_59 | Brain | WT | Saline |
SA338030 | WTS_58 | Brain | WT | Saline |
SA338031 | WTS_51 | Brain | WT | Saline |
SA338032 | WTS_31 | Brain | WT | Saline |
SA338033 | WTS_39 | Brain | WT | Saline |
SA338034 | WTS_53 | Brain | WT | Saline |
Showing results 1 to 20 of 20 |