| First Author | Ho WY | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 11 | Pages | 108152 |
| PubMed ID | 37920668 | Mgi Jnum | J:342179 |
| Mgi Id | MGI:7546567 | Doi | 10.1016/j.isci.2023.108152 |
| Citation | Ho WY, et al. (2023) FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons. iScience 26(11):108152 |
| abstractText | MicroRNAs (miRNAs) modulate mRNA expression, and their deregulation contributes to various diseases including amyotrophic lateral sclerosis (ALS). As fused in sarcoma (FUS) is a causal gene for ALS and regulates biogenesis of miRNAs, we systematically analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand how FUS-dependent miRNA deregulation contributes to ALS. miRNA profiling identified differentially expressed miRNAs between different central nervous system (CNS) regions as well as disease states. Among the up-regulated miRNAs, miR-1197 targets the pro-survival pseudokinase Trib2. A reduced TRIB2 expression was observed in iPSC-derived motor neurons from ALS patients. Pharmacological stabilization of TRIB2 protein with a clinically approved cancer drug rescues the survival of iPSC-derived human motor neurons, including those from a sporadic ALS patient. Collectively, our data indicate that miRNA profiling can be used to probe the molecular mechanisms underlying selective vulnerability, and TRIB2 is a potential therapeutic target for ALS. |
