| Autor: |
Wan Yun Ho, Li-Ling Chak, Jin-Hui Hor, Fujia Liu, Sandra Diaz-Garcia, Jer-Cherng Chang, Emma Sanford, Maria J. Rodriguez, Durgadevi Alagappan, Su Min Lim, Yik-Lam Cho, Yuji Shimizu, Alfred Xuyang Sun, Sheue-Houy Tyan, Edward Koo, Seung Hyun Kim, John Ravits, Shi-Yan Ng, Katsutomo Okamura, Shuo-Chien Ling |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 26, Iss 11, Pp 108152- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.108152 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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