Dokumentdetails
ID
doi:10.1186/s40478-022-01360-5...
Autor
Ding, Qiao Kesavan, Kaamini Lee, Kah Meng Wimberger, Elyse Robertson, Thomas Gill, Melinder Power, Dominique Chang, Jeryn Fard, Atefeh T. Mar, Jessica C. Henderson, Robert D. Heggie, Susan McCombe, Pamela A. Jeffree, Rosalind L. Colditz, Michael J. Hilliard, Massimo A. Ng, Dominic C. H. Steyn, Frederik J. Phillips, William D. Wolvetang, Ernst J. Ngo, Shyuan T. Noakes, Peter G.Langue
enEditor
BioMed Central
Kategorie
Neurology
Jahr
2022
Auflistungsdatum
08.12.2022
Schlüsselwörter
amyotrophic lateral sclerosis als neuromuscular junction musk agrin motor neurons acetylcholine receptors patients muscle mndZusammenfassung
A central event in the pathogenesis of motor neuron disease (MND) is the loss of neuromuscular junctions (NMJs), yet the mechanisms that lead to this event in MND remain to be fully elucidated.
Maintenance of the NMJ relies upon neural agrin ( n -agrin) which, when released from the nerve terminal, activates the postsynaptic Muscle Specific Kinase (MuSK) signaling complex to stabilize clusters of acetylcholine receptors.
Here, we report that muscle from MND patients has an increased proportion of slow fibers and muscle fibers with smaller diameter.
Muscle cells cultured from MND biopsies failed to form large clusters of acetylcholine receptors in response to either non-MND human motor axons or n -agrin.
Furthermore, levels of expression of MuSK, and MuSK-complex components: LRP4, Caveolin-3, and Dok7 differed between muscle cells cultured from MND patients compared to those from non-MND controls.
To our knowledge, this is the first time a fault in the n -agrin-LRP4-MuSK signaling pathway has been identified in muscle from MND patients.
Our results highlight the n -agrin-LRP4-MuSK signaling pathway as a potential therapeutic target to prolong muscle function in MND.
Ding, Qiao,Kesavan, Kaamini,Lee, Kah Meng,Wimberger, Elyse,Robertson, Thomas,Gill, Melinder,Power, Dominique,Chang, Jeryn,Fard, Atefeh T.,Mar, Jessica C.,Henderson, Robert D.,Heggie, Susan,McCombe, Pamela A.,Jeffree, Rosalind L.,Colditz, Michael J.,Hilliard, Massimo A.,Ng, Dominic C. H.,Steyn, Frederik J.,Phillips, William D.,Wolvetang, Ernst J.,Ngo, Shyuan T.,Noakes, Peter G., 2022, Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease, BioMed Central
