Reference - Detail
| RRC ID | 80816 |
|---|---|
| Author | Wong CH, Rahat A, Chang HC. |
| Title | Fused in sarcoma regulates glutamate signaling and oxidative stress response. |
| Journal | Free Radic Biol Med |
| Abstract |
Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor GLR-1. We found that fust-1 ALS mutations act as loss-of-function in SOD-1 and VGLUT/EAT-4 phenotypes, whereas the fust-1 ALS mutations act as gain-of-function in redox homeostasis and the microbe-induced oxidative stress response. We hypothesized that FUST-1 is a link between glutamate signaling and SOD-1. Our results may provide new insights into the human ALS alleles and their roles in pathological mechanisms that lead to ALS. |
| Volume | 210 |
| Pages | 172-182 |
| Published | 2024-1-1 |
| DOI | 10.1016/j.freeradbiomed.2023.11.015 |
| PII | S0891-5849(23)01116-4 |
| PMID | 38007141 |
| PMC | PMC10872661 |
| MeSH | Amyotrophic Lateral Sclerosis* / genetics Amyotrophic Lateral Sclerosis* / pathology Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Disease Models, Animal Glutamates / metabolism Humans Mutation Oxidation-Reduction Oxidative Stress / genetics RNA-Binding Protein FUS* / genetics RNA-Binding Protein FUS* / metabolism Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Superoxide Dismutase-1 / genetics |
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| The most frequently cited source | News |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4439 tm776 |