Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy
| Autor: | Hunter, Gillian, Powis, Rachael A., Jones, Ross A., Groen, Ewout J.N., Shorrock, Hannah K., Lane, Fiona M., Zheng, Yinan, Sherman, Diane L., Brophy, Peter J., Gillingwater, Thomas H. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Motor Neurons
Neuromuscular Junction Mice Transgenic Articles Neuromuscular Diseases Survival of Motor Neuron 1 Protein nervous system diseases Muscular Atrophy Spinal Survival of Motor Neuron 2 Protein Disease Models Animal Mice nervous system Spinal Cord Nerve Degeneration Animals Schwann Cells Neuroglia Myelin Sheath |
| Zdroj: | Human Molecular Genetics Hunter, G, Powis, R A, Jones, R A, Groen, E J N, Shorrock, H K, Lane, F M, Zheng, Y, Sherman, D L, Brophy, P J & Gillingwater, T H 2016, ' Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy ', Human Molecular Genetics, vol. 25, no. 13, pp. 2853–2861 . https://doi.org/10.1093/hmg/ddw141 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddw141 |
| Popis: | Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn-/-;SMN2tg/0;SMN1SC). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|