![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Preprint)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
11MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
7MB |
| Item Type: | Preprint |
|---|---|
| Title: | Neuromuscular dysfunction in patient-derived FUS(R244RR)-ALS iPSC model via axonal downregulation of neuromuscular junction proteins |
| Creators Name: | von Kuegelgen, N., Ludwik, K., Mendonsa, S., Roemer, C., Becher, E., Breimann, L., Strauch, M., Mari, T., Mongellaz, S., Zuckerman, B., 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. Here, we established a FUS(R244RR)-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: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2024.08.17.607965 |
| Date: | 17 August 2024 |
| Official Publication: | https://doi.org/10.1101/2024.08.17.607965 |
Repository Staff Only: item control page
