Article
Biology
Hidehiko Okuma, Jeffrey M. Hord, Ishita Chandel, David Venzke, Mary E. Anderson, Ameya S. Walimbe, Soumya Joseph, Zeita Gastel, Yuji Hara, Fumiaki Saito, Kiichiro Matsumura, Kevin P. Campbell
Summary: Post-translational processing and O-glycosylation are critical for the function of Dystroglycan (DG) as a receptor for extracellular matrix (ECM) proteins. Our study demonstrates the importance of protein O-mannose kinase (POMK) and alpha-DGN in the synthesis of matriglycan by LARGE1.
Article
Biochemistry & Molecular Biology
Pedro Monagas-Valentin, Robert Bridger, Ishita Chandel, Melissa Koff, Boris Novikov, Patrick Schroeder, Lance Wells, Vladislav Panin
Summary: Mutations in POMTs cause brain defects and muscular dystrophies due to abnormal glycosylation of alpha-Dg. PTP69D is identified as a gene that interacts with POMTs to produce the abdomen rotation phenotype. PTP69D is required for larval sensory axon wiring and is a substrate of POMT-mediated O-mannosylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Shama R. Iyer, Sameer B. Shah, Richard M. Lovering
Summary: The neuromuscular junction plays a crucial role in neuromuscular performance, influencing the development and treatment of neuromuscular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Travis D. Carney, Rucha Y. Hebalkar, Evgeniia Edeleva, Ibrahim Omer cicek, Halyna R. Shcherbata
Summary: Deficiencies in the human dystrophin glycoprotein complex (DGC) cause muscular dystrophies, which are incurable disorders associated with muscle, brain, and eye abnormalities. This study investigated the transcriptomic changes in mutants of four DGC components under stress conditions, revealing the novel function of DGC in stress-response signaling. The findings provide new insights into the etiology of muscular dystrophy symptoms and potential treatment directions.
DISEASE MODELS & MECHANISMS
(2023)
Article
Chemistry, Medicinal
Lizzia Raffaghello, Elisa Principi, Serena Baratto, Chiara Panicucci, Sara Pintus, Francesca Antonini, Genny Del Zotto, Andrea Benzi, Santina Bruzzone, Paolo Scudieri, Carlo Minetti, Elisabetta Gazzerro, Claudio Bruno
Summary: In this study, the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079, was evaluated in limb-girdle muscular dystrophy R3. The results showed that the P2X7 antagonist improved clinical parameters, reduced muscle inflammation and fibrosis, and upregulated immunosuppressive regulatory T cells.
Review
Biochemistry & Molecular Biology
Motoi Kanagawa
Summary: Dystroglycanopathy is a group of muscular dystrophies caused by abnormal glycosylation of dystroglycan, with diverse clinical symptoms ranging from congenital to adult-onset types. Research in the 2010s has identified the sugar chain structure and functions of causative gene products, created various model mice for studying pathological mechanisms, and proposed treatment strategies based on glycosylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alan Rawls, Bridget K. Diviak, Cameron I. Smith, Grant W. Severson, Sofia A. Acosta, Jeanne Wilson-Rawls
Summary: Muscular dystrophies are genetic muscle-wasting disorders characterized by chronic inflammation and fibrotic scarring in muscle tissue. Duchenne muscular dystrophy, the most common form, is typically treated with anti-inflammatory glucocorticoids; however, their long-term use is limited by adverse side effects. Developing new pharmacotherapeutic approaches to reduce muscle damage and promote repair is crucial.
Article
Chemistry, Multidisciplinary
Eri Sasaki, Yoshihiro Hayashi, Yuka Kimura, Sanae Sashida, Nobuhito Hamano, Kei Nirasawa, Keisuke Hamada, Fumihiko Katagiri, Yamato Kikkawa, Takaaki Sakai, Akihiro Yoshida, Masahiro Kawada, Shin-ichi Hirashima, Tsuyoshi Miura, Yoko Endo-Takahashi, Motoyoshi Nomizu, Yoichi Negishi
Summary: The study focused on developing A2G80-modified liposomes as a muscle-targeting nanocarrier for Duchenne muscular dystrophy (DMD) treatment. Through overlay assays, it was demonstrated that A2G80-LSP-Lip had an affinity for muscle tissue in mice and efficiently accumulated in muscle tissue when administered through the tail vein to DMD model mice. These results suggest that A2G80-LSP-Lip may serve as a useful tool for DMD treatment via systemic administration.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Cell Biology
Ella Dunn, Joern R. Steinert, Aelfwin Stone, Virender Sahota, Robin S. B. Williams, Stuart Snowden, Hrvoje Augustin
Summary: This study investigates the role of specific medium-chain fatty acids (MCFAs) in reversing pathogenic outcomes in C9ALS/FTD using a Drosophila melanogaster model. The results show that two MCFAs, nonanoic acid and 4-methyloctanoic acid, can improve motor function and neuromuscular junction degeneration in C9 larvae, although their mechanisms of action are different. The findings provide insights into potential therapeutic targets and treatments for ALS.
Article
Materials Science, Multidisciplinary
Ersilia Fornetti, Stefano Testa, Francesca De Paolis, Claudia Fuoco, Sergio Bernardini, Victorio Pozo Devoto, Gorazd Bernard Stokin, Sara Maria Giannitelli, Alberto Rainer, Anne Bigot, Carmine Zoccali, Jacopo Baldi, Doriana Sandona, Roberto Rizzi, Claudia Bearzi, Giancarlo Forte, Stefano Cannata, Cesare Gargioli
Summary: This article introduces an approach to construct an in vitro neuromuscular junction (NMJ) using a microfluidic chip, aiming to establish a reliable and predictive human model to investigate synapse detriment in α-sarcoglycanopathy.
ADVANCED MATERIALS TECHNOLOGIES
(2022)
Article
Biochemistry & Molecular Biology
Alec Wright, Arielle Hall, Tara Daly, Tatiana Fontelonga, Sarah Potter, Caitlin Schafer, Andrew Lindsley, Christina Hung, Olaf Bodamer, Emanuela Gussoni
Summary: Kabuki syndrome is a rare genetic disorder caused by mutations in histone modifier genes, leading to complex phenotypes. Research on the consequences of loss of KMT2D function in muscles of mice and humans revealed that epigenetic changes associated with the disorder can be reversed in a suitable physiological environment.
Review
Biochemistry & Molecular Biology
Adel E. E. Khairullin, Sergey N. N. Grishin, Ayrat U. U. Ziganshin
Summary: The purine signaling system, represented by purine and pyrimidine nucleotides and nucleosides, plays a role through the adenosine, P2X and P2Y receptor families. While P2 receptors have a minor role in physiological conditions, they become more significant in certain pathophysiological conditions, functioning as dominant signaling molecules. The diversity and distribution of P2 receptors make them an attractive target for new mechanism drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Jackie L. L. McCourt, Kristen M. M. Stearns-Reider, Hafsa Mamsa, Pranav Kannan, Mohammad Hossein Afsharinia, Cynthia Shu, Elizabeth M. M. Gibbs, Kara M. M. Shin, Yerbol Z. Z. Kurmangaliyev, Lauren R. R. Schmitt, Kirk C. C. Hansen, Rachelle H. H. Crosbie
Summary: This study identified the compensatory action of sarcospan (SSPN) overexpression in dystrophin deficiency, showing that it enhances cell-ECM bidirectional communication and protects muscle from contraction-induced injury. The overexpression of SSPN resulted in upregulation of signaling molecules associated with cytoskeleton organization, mechanotransduction, and ECM components.
Article
Clinical Neurology
Pinki Munot, Nadine McCrea, Silvia Torelli, Adnan Manzur, Caroline Sewry, Darren Chambers, Lucy Feng, Pierpaolo Ala, Irina Zaharieva, Nicola Ragge, Helen Roper, Tamas Marton, Phil Cox, Miroslav P. Milev, Wen-Chen Liang, Shinsuke Maruyama, Ichizo Nishino, Michael Sacher, Rahul Phadke, Francesco Muntoni
Summary: This study presents five cases of early-onset TRAPPC11-related muscular dystrophy, with muscle pathology findings in all cases, post-mortem brain pathology findings in one case, and membrane trafficking assays in another. The findings suggest that recessive mutations in TRAPPC11 are linked to muscular dystrophies with hypoglycosylation of alpha-dystroglycan, and structural cerebellar involvement similar to that seen in N-linked congenital disorders of glycosylation.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
M. Osman Sheikh, Chantelle J. Capicciotti, Lin Liu, Jeremy Praissman, Dahai Ding, Daniel G. Mead, Melinda A. Brindley, Tobias Willer, Kevin P. Campbell, Kelley W. Moremen, Lance Wells, Geert-Jan Boons
Summary: Matriglycan plays a critical role in protein binding and viral infection, and its length can be adjusted accordingly. This finding contributes to a better understanding of the interaction between cells and viruses.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Russo, Pragya Goel, E. J. Brace, Chris Buser, Dion Dickman, Aaron DiAntonio
Article
Neurosciences
Daniel W. Summers, Erin Frey, Lauren J. Walker, Jeffrey Milbrandt, Aaron DiAntonio
MOLECULAR NEUROBIOLOGY
(2020)
Article
Neurosciences
Yo Sasaki, Thomas M. Engber, Robert O. Hughes, Matthew D. Figley, Tong Wu, Todd Bosanac, Rajesh Devraj, Jeffrey Milbrandt, Raul Krauss, Aaron DiAntonio
EXPERIMENTAL NEUROLOGY
(2020)
Article
Cell Biology
Kwang Woo Ko, Jeffrey Milbrandt, Aaron DiAntonio
JOURNAL OF CELL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
John C. Bramley, Alex L. Yenkin, Mark A. Zaydman, Aaron DiAntonio, Jeffrey D. Milbrandt, William J. Buchser
Article
Multidisciplinary Sciences
Chen Shen, Mihir Vohra, Pengfei Zhang, Xianrong Mao, Matthew D. Figley, Jian Zhu, Yo Sasaki, Hao Wu, Aaron DiAntonio, Jeffrey Milbrandt
Summary: Axon degeneration is regulated by the protein SARM1, with its self-inhibition being a crucial mechanism for maintaining neuronal health. Multiple domain interfaces are involved in SARM1 autoinhibition, and mutations disrupting these interfaces can lead to constitutive activation of SARM1 and subsequent neuronal degeneration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Hailun Li, Lorenzo Lones, Aaron DiAntonio
Summary: The study reveals that an octopaminergic circuit regulates the buffering capacity of glial cells in Drosophila by modulating different types of octopaminergic G-protein-coupled receptors. This insight provides a new approach for the treatment of epilepsy by targeting glial cells.
Article
Plant Sciences
Samuel Eastman, Thomas Smith, Mark A. Zaydman, Panya Kim, Samuel Martinez, Neha Damaraju, Aaron DiAntonio, Jeffrey Milbrandt, Thomas E. Clemente, James R. Alfano, Ming Guo
Summary: HopAM1 is a Pseudomonas syringae DC3000 type III effector that suppresses plant immunity and induces cell death by hydrolyzing NAD(+). It has catalytic activity to manipulate endogenous NAD(+) metabolism in plants and promote pathogenesis. The TIR domain of HopAM1 shows a unique catalytic specificity compared to other NAD(+) hydrolases, allowing pathogens to exploit this activity for immune suppression and virulence.
Article
Biology
Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron DiAntonio
Summary: By using live imaging of mouse sensory neurons with single axon resolution, researchers discovered an ordered sequence of cellular events downstream of SARM1 activity, including loss of cellular ATP, defects in mitochondrial movement and depolarization, followed by calcium influx, externalization of phosphatidylserine, and loss of membrane permeability, leading to catastrophic axonal self-destruction.
Article
Genetics & Heredity
E. J. Brace, Kow Essuman, Xianrong Mao, John Palucki, Yo Sasaki, Jeff Milbrandt, Aaron DiAntonio
Summary: SARM1 is involved in axon loss and inhibition of SARM1 has therapeutic potential for neurodegenerative disorders. This study reveals that SARM1 acts as an enzyme and regulates developmental signaling pathways.
Article
Biology
Mark A. Zaydman, Alexander S. Little, Fidel Haro, Valeryia Aksianiuk, William J. Buchser, Aaron DiAntonio, Jeffrey Gordon, Jeffrey Milbrandt, Arjun S. Raman, Nir Ben-Tal
Summary: Cellular behaviors are determined by layers of molecular interactions, and by analyzing the statistical patterns of proteome variations in diverse bacteria, we can define hierarchical networks of protein interactions that reflect the emergence of complex bacterial phenotypes. Our approach, SCALES, allows for the interrogation of genotype-phenotype relationships in bacteria and has been validated through gene-set enrichment analysis and comparison to existing databases.
Article
Medicine, Research & Experimental
Yurie Sato-Yamada, Amy Strickland, Yo Sasaki, Joseph Bloom, Aaron DiAntonio, Jeffrey Milbrandt
Summary: Based on the study of SARM1 in a CMT2A model, SARM1 inhibitors may be potential therapeutic candidates for the treatment of CMT2A and other neurodegenerative diseases with mitochondrial pathology.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Genetics & Heredity
Lorenzo Lones, Aaron Di Antonio
Summary: The research found that enhancing glial cells' ability to regulate lithium ions can suppress seizures. The study also found that the Wnk kinase regulates the buffering of lithium ions in glial cells through the transcription factor Fray, and overexpression of the Fray gene can effectively suppress seizure behavior in multiple epilepsy models. Finally, the study identified cortex glia as a key cell type in the susceptibility to seizures.
Article
Biology
Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron DiAntonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt
Article
Medicine, Research & Experimental
Stefanie Geisler, Ryan A. Doan, Galen C. Cheng, Aysel Cetinkaya-Fisgin, Shay X. Huang, Ahmet Hoke, Jeffrey Milbrandt, Aaron DiAntonio