Neuromuscular Junction Formation, Aging, and Disorders

Li, Lei; Xiong, Wen-Cheng; Mei, Lin

doi:10.1146/annurev-physiol-022516-034255

Cited by 267 publications

(285 citation statements)

References 167 publications

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“…Thus, it is not surprising that the loss or dysfunction of motor neurons, muscle fibers and PSCs invariably causes deleterious changes at NMJs. For example, the NMJ degenerates in amyotrophic lateral sclerosis (ALS), as well as in the spectrum of myasthenia gravis and muscular dystrophies [2,3]. These are diseases that invariably compromise the function and health of motor neurons, muscle fibers and PSCs.…”

Section: Introductionmentioning

confidence: 99%

NMJ maintenance and repair in aging

Taetzsch

Valdez

2018

Current Opinion in Physiology

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As the final output of the somatic nervous system, the neuromuscular junction (NMJ) is essential for all voluntary movements. The NMJ is also necessary for connected cells to function and survive. Because of this central role, much effort has been devoted to understanding the effects of aging, diseases, and injuries on the NMJ. These efforts have revealed a close relationship between aberrant changes at NMJs and its three cellular components - the presynaptic site on motor axons, the postsynaptic region on muscle fibers and perisynaptic Schwann cells. Here, we review the morphological and molecular changes associated with aging NMJs in rodents and humans. We also provide an overview of factors with potential roles in maintaining and repairing adult and aged NMJs.

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Section: Introductionmentioning

confidence: 99%

NMJ maintenance and repair in aging

Taetzsch

Valdez

2018

Current Opinion in Physiology

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“…[33][34][35] In practice, eculizumab, a humanized monoclonal antibody that binds to C5, preventing formation of a C5b-induced MAC, can be prescribed for the treatment of generalized AChR-MG. 36 The second mechanism involved in the pathogenesis of AChR-MG has also been shown with animal models. 40,41 In 2001, autoantibodies against MuSK were first identified in the plasma of patients with MG who were seronegative for AChR antibodies. Thus, available AChR at NMJ are reduced if accelerated degradation is not compensated sufficiently by increased AChR synthesis and expression at NMJ.…”

Section: Animal Models Of Achr-mgmentioning

confidence: 99%

Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications

Mori

Shigemoto

2019

Clinical & Exp Neuroim

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Myasthenia gravis (MG) is an autoimmune disease characterized by ptosis, fatigue and muscle weakness, caused by the association of pathogenic autoantibodies with postsynaptic membrane proteins at neuromuscular junctions. Although various autoantibodies have been found in sera from patients with MG, causal relationships with MG have not been shown for most antibodies. Establishment of the pathogenicity of candidate antibodies with experimental animal models of myasthenia gravis is indispensable. The pathogenicity of autoantibodies against acetylcholine receptors and musclespecific kinase has been confirmed by active immunization with purified antigens or by passive transfer of autoantibodies from patients with MG. Furthermore, animal models of MG have shown not only the pathogenic mechanisms underlying the manifestation of muscle weakness and atrophy observed in patients with MG, but also the efficacy of novel therapies and the adverse effects of therapeutic drugs. Here, we review the contributions of animal MG models to the elucidation of the pathogenic mechanisms of MG and the development of medications for the disease.

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“…The NMJ is a classical chemical synapse where both presynaptic and postsynaptic membranes are highly differentiated . Axon terminals form active zones for docking ACh‐containing vesicles and facilitating their release.…”

Section: Nmj Formation and Maintenancementioning

confidence: 99%

“…Less is understood about the signals from muscles to motor nerves. Nevertheless, many molecules have been identified to regulate presynaptic differentiation at the NMJ, including FGF7/10/22, collagens IV and XIII, GDNF, and laminin β2 . β‐Catenin in muscle is critical for motoneuron differentiation .…”

Section: Nmj Formation and Maintenancementioning

confidence: 99%

Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis

Yan

Xing

Xiong

et al. 2018

Annals of the New York Academy of Sciences

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Myasthenia gravis (MG) is a common disorder that affects the neuromuscular junction. It is caused by antibodies against acetylcholine receptor and muscle-specific tyrosine kinase; however, some MG patients do not have antibodies against either of the proteins. Recent studies have revealed antibodies against agrin and its receptor LRP4-both critical for neuromuscular junction formation and maintenance-in MG patients from various populations. Results from experimental autoimmune MG animal models indicate that anti-LRP4 antibodies are causal to MG. Clinical studies have begun to reveal the significance of the new biomarkers. With their identification, MG appears to be a complex disease entity that can be classified into different subtypes with different etiology, each with unique symptoms. Future systematic studies of large cohorts of well-diagnosed MG patients are needed to determine whether each subtype of patients would respond to different therapeutic strategies. Results should contribute to the goal of precision medicine for MG patients. Anti-agrin and anti-LRP4 antibodies are also detectable in some patients with amyotrophic lateral sclerosis or Lou Gehrig's disease; however, whether they are a cause or response to the disorder remains unclear.

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Neuromuscular Junction Formation, Aging, and Disorders

Cited by 267 publications

References 167 publications

NMJ maintenance and repair in aging

NMJ maintenance and repair in aging

Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications

Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis

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