The neuromuscular junction (NMJ) is a chemical synapse formed between a presynaptic motor neuron and a postsynaptic muscle cell. NMJs in most vertebrate species share many essential features; however, some differences distinguish human NMJs from others. This review will describe the pre- and postsynaptic structures of human NMJs and compare them to NMJs of laboratory animals. We will focus on age-dependent declines in function and changes in the structure of human NMJs. Furthermore, we will describe insights into the aging process revealed from mouse models of accelerated aging. In addition, we will compare aging phenotypes to other human pathologies that cause impairments of pre- and postsynaptic structures at NMJs. Finally, we will discuss potential intervention approaches for attenuating age-related NMJ dysfunction and sarcopenia in humans.
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http://dx.doi.org/10.3389/fnmol.2020.568426 | DOI Listing |
Toxins (Basel)
November 2024
Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS/Université Paris-Sud, 91198 Gif-sur-Yvette, Cedex, France.
Botulinum neurotoxin type-A (BoNT/A), which blocks quantal acetylcholine (ACh) release at the neuromuscular junction (NMJ), has demonstrated its efficacy in the symptomatic treatment of blepharospasm. In 3.89% of patients treated for blepharospasm at Tenon Hospital, BoNT/A was no longer effective in relieving the patient's symptoms, and a partial upper myectomy of the muscle was performed.
View Article and Find Full Text PDFExp Neurol
February 2025
Department of Developmental Biology, Washington University School of Medicine, St. Louis 63110, United States; Needleman Center for Neurometabolism and Axonal Therapeutics, St. Louis 63110, United States. Electronic address:
Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation.
View Article and Find Full Text PDFCurr Opin Genet Dev
August 2024
Max Delbrück Center, Berlin 13125, Germany. Electronic address:
Understanding the development and function of the human neuromuscular system is crucial for deciphering the mechanisms of neuromuscular disorders and developing effective therapies. However, limitations of animal models necessitate the development of human-specific in vitro models to study such complex diseases effectively. Here, we discuss different approaches for in vitro neuromuscular junction (NMJ) modeling: complex self-organized models that rely on the inherent abilities of cells to form NMJs based on embryonic developmental principles and assembled models that depend on integrating different cell types for controlled NMJ formation.
View Article and Find Full Text PDFCold Spring Harb Perspect Biol
January 2025
Département de neurosciences, Université de Montréal, Montréal, Québec H3C 3J7, Canada
The neuromuscular junction (NMJ) is a highly reliable synapse to carry the control of the motor commands of the nervous system over the muscles. Its development, organization, and synaptic properties are highly structured and regulated to support such reliability and efficacy. Yet, the NMJ is also highly plastic, able to react to injury, and able to adapt to changes.
View Article and Find Full Text PDFJ Orthop Translat
May 2024
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.
The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies.
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