1. Engineered agrin attenuates the severity of experimental autoimmune myasthenia gravis.
- Author
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Li Z, Li M, Wood K, Hettwer S, Muley SA, Shi FD, Liu Q, and Ladha SS
- Subjects
- Action Potentials physiology, Agrin biosynthesis, Agrin chemistry, Animals, Autoantibodies metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Electromyography, Female, Freund's Adjuvant toxicity, Gene Expression Regulation drug effects, Membrane Glycoproteins metabolism, Muscle, Skeletal pathology, Muscular Atrophy etiology, Muscular Atrophy therapy, Nerve Tissue Proteins metabolism, Neurofibromin 1 metabolism, Neuromuscular Junction pathology, Peptide Fragments biosynthesis, Peptide Fragments chemistry, Rats, Rats, Inbred Lew, Receptors, Cholinergic immunology, Receptors, Cholinergic metabolism, Agrin therapeutic use, Immunization adverse effects, Myasthenia Gravis, Autoimmune, Experimental drug therapy, Myasthenia Gravis, Autoimmune, Experimental pathology, Peptide Fragments therapeutic use
- Abstract
Introduction: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG)., Methods: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days., Results: We showed that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats., Discussion: We demonstrated that NT-1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK) in EAMG rats. Muscle Nerve 57: 814-820, 2018., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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