Injection of a soluble fragment of neural agrin (NT-1654) considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction
| Autor: | Shuo Lin, Monika Haubitz, Filippo Oliveri, Jan Wim Vrijbloed, Markus A. Rüegg, Stefan Kucsera, Stefan Hettwer, Ruggero Fariello |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Sarcopenia
Mouse Muscle Fibers Skeletal lcsh:Medicine Biochemistry Muscular Dystrophies Extracellular matrix Motor Neuron Diseases Mice Drug Discovery Receptors Cholinergic Receptor lcsh:Science Denervation Multidisciplinary Agrin Serine Endopeptidases Anatomy Animal Models Neuromuscular Diseases Sciatic Nerve Cell biology Slow-Twitch Muscle Fiber medicine.anatomical_structure Phenotype Neurology Medicine Sciatic nerve Research Article animal structures Nerve Crush Neuromuscular Junction Biology Signaling Pathways Neuromuscular junction Injections Model Organisms medicine Animals Humans Muscle Strength Muscle Skeletal Motor Systems lcsh:R Body Weight medicine.disease Mice Inbred C57BL HEK293 Cells Solubility nervous system lcsh:Q Molecular Neuroscience Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 2, p e88739 (2014) |
| Popis: | Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO) mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders. |
| Databáze: | OpenAIRE |
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