![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
21MB |
![[thumbnail of Supplementary Data]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Data)
12MB |
| Item Type: | Article |
|---|---|
| Title: | Neuromuscular dysfunction in patient-derived FUS(R244RR)-ALS iPSC model via axonal downregulation of neuromuscular junction proteins |
| Creators Name: | von Kügelgen, N., Ludwik, K.A., Mendonsa, S., Römer, C., Becher, E., Breimann, L., Strauch, M., Mari, T., Mongellaz, S., Zuckerman, B., Efendic, F., Grexa, N., Oliveras-Martinez, A., Woehler, A., Selbach, M., La Bella, V., Ulitsky, I. and Chekulaeva, M. |
| Abstract: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive degeneration of motor neurons, ultimately resulting in death due to respiratory failure. A common feature among ALS cases is the early loss of axons, pointing to defects in axonal transport and translation as initial disease indicators. ALS is associated with mutations in RNA-binding proteins, such as FUS (Fused in Sarcoma). Here, we established a FUSR244RR-ALS hiPSC-derived model that recapitulates the motor neuron survival and muscle contractility defects characteristic of ALS patients. Analysis of the protein and mRNA expression profiles in axonal and somatodendritic compartments of ALS-afflicted and isogenic control motor neurons revealed a selective downregulation of proteins essential for the neuromuscular junction function in FUS-ALS axons. Furthermore, analysis of FUS CLIP and RIP data showed that FUS binds mRNAs encoding these proteins. This work shed light on the pathogenic mechanisms of ALS and emphasized the importance of axonal gene expression analysis in elucidating the mechanisms of neurodegenerative disorders. |
| Keywords: | Motor Neuron, mRNA Localization, RNA-Binding Proteins (RBPs), ALS |
| Source: | NAR Molecular Medicine |
| ISSN: | 2976-856X |
| Publisher: | Oxford University Press |
| Volume: | 2 |
| Number: | 2 |
| Page Range: | ugaf005 |
| Date: | April 2025 |
| Official Publication: | https://doi.org/10.1093/narmme/ugaf005 |
Repository Staff Only: item control page
