Article
Cell Biology
Jakob Proemer, Cinzia Barresi, Ruth Herbst
Summary: Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development and its activation and signaling are tightly regulated. Recent studies using omics techniques have contributed to a better understanding of MuSK signaling. Impaired MuSK signaling causes muscle weakness, but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling, as well as the role of MuSK in non-muscle tissue.
CELLULAR SIGNALLING
(2023)
Article
Geriatrics & Gerontology
Jedd Pratt, Giuseppe De Vito, Marco Narici, Ricardo Segurado, Ludmilla Pessanha, Jackie Dolan, Judith Conroy, Colin Boreham
Summary: This study confirms the relevance of plasma CAF as a biomarker for sarcopenia, showing significant associations with muscle mass and elevated levels in sarcopenic individuals. Gender differences were observed, with males showing elevated CAF levels in low grip strength or low ALM, while only low ALM in females had significantly raised CAF concentrations compared to healthy controls.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Geriatrics & Gerontology
Kuniyasu Kamiya, Takahiro Tachiki, Yuho Sato, Katsuyasu Kouda, Etsuko Kajita, Junko Tamaki, Sadanobu Kagamimori, Masayuki Iki
Summary: This study found that CAF110 was associated with the presence and incidence of low muscle mass, but not low muscle strength.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Engineering, Biomedical
Ji Hyun Kim, In Kap Ko, Myung Jae Jeon, Ickhee Kim, Margaret Maria Vanschaayk, Anthony Atala, James J. Yoo
Summary: Efficient innervation is crucial for successful grafting and functional recovery of bioengineered skeletal muscle constructs. In this study, a 3D bioprinted human skeletal muscle construct with pre-formed AChR clusters is developed and shown to accelerate innervation in vivo, leading to functional muscle reconstruction in a rat model of pelvic floor muscle injury.
ACTA BIOMATERIALIA
(2021)
Article
Geriatrics & Gerontology
Jedd Pratt, Laura Whitton, Anthony Ryan, Thorhildur Juliusdottir, Jackie Dolan, Judith Conroy, Marco Narici, Giuseppe De Vito, Colin Boreham
Summary: The genes AGRN and PRSS12 are associated with muscle mass and strength, indicating their importance in maintaining muscle health during aging. This study provides novel evidence supporting the role of the neuromuscular junction (NMJ) in sarcopenia phenotypes.
Article
Developmental Biology
Lauren J. Walker, Rebecca A. Roque, Maria F. Navarro, Michael Granato
Summary: Using a zebrafish pectoral fin model, the study shows similarities in the development of neuromuscular synapses between axial and appendicular muscles, but differences in the MuSK, Agrin, and Lrp4 signaling pathways. This highlights distinct differences between axial and appendicular synapse development.
Article
Biochemistry & Molecular Biology
Paul Tawa, Lei Zhang, Essam Metwally, Yan Hou, Mark A. McCoy, W. Michael Seganish, Rumin Zhang, Emily Frank, Payal Sheth, Jennifer Hanisak, Christopher Sondey, David Bauman, Aileen Soriano
Summary: cGMP-dependent protein kinase (PKG) is an important drug target for cardiovascular diseases. In this study, a novel series of activators were identified that can directly bind and enhance the kinase activity of PKG1. These activators mimic the effect of cGMP on PKG1 by modulating its kinetic parameters and binding affinity for cGMP. They act by binding to an allosteric site near the regulatory domain of PKG1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Developmental Biology
Jun Yu, Marilyn Janice Oentaryo, Chi Wai Lee
Summary: The study demonstrates the essential role of local protein synthesis in presynaptic differentiation at developing neuromuscular junctions. Newly synthesized proteins play a crucial role at agrin bead-neurite contacts. Axonal MT1-MMP translation is shown to be vital in mediating agrin-induced presynaptic differentiation, in addition to the recognized long-range transport of MT1-MMP proteins.
Review
Cardiac & Cardiovascular Systems
Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F. Luscher, Rodolphe Fischmeister, David A. Kass, John C. Burnett, Adrian J. Hobbs, Harald H. H. W. Schmidt
Summary: Mechanism-based therapy focused on understanding disease pathways at the molecular level is still rare in cardiovascular medicine, but recent drug developments centered around cGMP offer promising personalized treatment options. By modulating cGMP synthesis or breakdown, these drugs show potential for protective effects across various cardiac conditions.
CARDIOVASCULAR RESEARCH
(2022)
Article
Clinical Neurology
Zheng Yu, Meiying Zhang, Hongyang Jing, Peng Chen, Rangjuan Cao, Jinxiu Pan, Bin Luo, Yue Yu, Brandy M. Quarles, Wencheng Xiong, Michael H. Rivner, Lin Mei
Summary: The study aimed to investigate the pathogenic role of human anti-LRP4/agrin antibodies in mice and found that the antibodies led to MG symptoms in the mice. The antibodies impaired neuromuscular junction function and disrupted agrin-dependent LRP4-MuSK interaction, providing insights into the pathogenic mechanisms of these antibodies.
Article
Clinical Neurology
Zheng Yu, Meiying Zhang, Hongyang Jing, Peng Chen, Rangjuan Cao, Jinxiu Pan, Bin Luo, Yue Yu, Brandy M. Quarles, Wencheng Xiong, Michael H. Rivner, Lin Mei
Summary: The study found that antibodies against LRP4/agrin from a patient with MG can induce MG symptoms in mice, including weight loss and muscle weakness. These antibodies impair the neuromuscular junction by interfering with agrin-dependent LRP4-MuSK interaction, leading to compromised neuromuscular transmission and fragmentation of the neuromuscular junction.
Article
Neurosciences
Taro Inoue, Bisei Ohkawara, Samira Bushra, Shunsuke Kanbara, Hiroaki Nakashima, Hiroyuki Koshimizu, Hiroyuki Tomita, Mikako Ito, Akio Masuda, Naoki Ishiguro, Shiro Imagama, Kinji Ohno
Summary: Zonisamide enhances agrin-dependent AChR clustering by upregulating the Nrg1/ErbB signaling pathways at the NMJ.
Article
Zoology
Wen-Yo Tu, Wentao Xu, Jianmin Zhang, Shuyuan Qi, Lei Bai, Chengyong Shen, Kejing Zhang
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by the loss of control of skeletal muscles. Degeneration of neuromuscular junctions (NMJs) is an early event in ALS. Poly-GA, the most abundant form of DPR in C9-ALS, is released from cells and impairs NMJs through inhibiting Agrin-MuSK signaling.
ZOOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Geriatrics & Gerontology
Martino V. Franchi, Francesca Badiali, Fabio Sarto, Patrick Mueller, Notger G. Mueller, Kathrin Rehfeld, Elena Monti, Debbie Rankin, Stefano Longo, Jon Lund, Anita Hoekelmann, Marco Narici
Summary: This study found that recreational dancing has stronger neuroprotective effects and can increase muscle function in older individuals compared to general fitness exercise training.