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Neuromuscular junction; a potential therapeutic target for sarcopenia

Shuuichi Mori, Ph.D.

Researcher (Geriatric Medicine)

Aging gradually causes a decrease in physical ability and the ease of carrying out daily tasks. The fundamental cause of these problems is an age-associated decline in skeletal muscle mass and function, a condition known as sarcopenia. With our increasingly aging society, prevention and treatment of sarcopenia is essential in order to reduce the risk of morbidity and mortality in the elderly. Therefore, research has focused on improving our understanding of the etiology of sarcopenia, which should lead to new methods being devised for preventing and treating this disability. The exact etiology of sarcopenia is not completely understood, but recent studies have focused on age-associated changes in the neuromuscular junction (NMJ). NMJ is a joint between motoneurons and skeletal muscle, and is composed of three regions: the presynaptic part (the motor nerve terminal), the synaptic cleft, and the postsynaptic part (the muscle membranes). The NMJ is a specialized structure with a number of properties that ensure effective neuromuscular transmission. Using an animal model of myasthenia gravis (MG) with antibodies against muscle-specific kinase (MuSK), an autoimmune disorder of the NMJ characterized by muscle weakness, we investigated the role of the NMJ in the pathogenesis of sarcopenia. Our studies indicate that the structure and function of the NMJ is important for maintaining muscle mass and strength, which suggests that the malfunction of the NMJ plays a role, at least in part, in the onset of sarcopenia. We believe that studying MG, caused by inhibition of MuSK, is a useful method for trying to resolve the pathogenic mechanisms of sarcopenia. Another approach in the search for unraveling a potential mechanism for maintaining NMJ structure and function is to develop biomarkers for the diagnosis of sarcopenia. Early detection of sarcopenia using such biomarkers is important for initiating treatment early in patients and for monitoring the efficacy of treatment continuously. In conclusion, the NMJ will become an important therapeutic target for sarcopenia in the future.

1. Mori S, Koshi K, Shigemoto K. The important role of the neuromuscular junction in maintaining muscle mass and strength. J Phys Fitness Sports Med 3: 111-114.2014.
2. Mori S, Shigemoto K. Mechanisms associated with the pathogenicity of antibodies against muscle-specific kinase in myasthenia gravis. Autoimmun Rev 12: 912-917, 2013.
3. Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, Desaki J, Kishi M, Konishi T, Nishino Y, Miyazawa A, Maruyama N, Shigemoto K. Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis. Am J Pathol 180: 798-810, 2012.