Article
Biochemistry & Molecular Biology
Lucas Bayones, Maria Jose Guerra-Fernandez, Fernando Hinostroza, Ximena Baez-Matus, Jacqueline Vasquez-Navarrete, Luciana Gallo, Sergio Parra, Agustin D. Martinez, Arlek Gonzalez-Jamett, Fernando D. Marengo, Ana M. Cardenas
Summary: Gain-of-function mutations of dynamin-2 result in centronuclear myopathy by impairing exocytosis, disrupting actin filament formation and impacting the plasmalemma expression of functional proteins in skeletal muscle cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kenshiro Fujise, Satoru Noguchi, Tetsuya Takeda
Summary: This review provides an overview of the functions of dynamin 2 and BIN1 in T-tubule biogenesis and discusses how their dysfunction in membrane remodelling leads to CNM pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Bungo Hirose, Kazuna Ikeda, Daisuke Yamamoto, Emiko Tsuda, Rika Yamauchi, Takayoshi Hozuki, Yoshiki Masuda, Tomihiro Imai
Summary: The study aimed to develop a simple and reliable technique for early diagnosis of critical illness myopathy (CIM) by evaluating excitation-contraction (E-C) coupling. The measurement of E-C coupling time (ECCT) was found to be an effective method to detect reduced muscle membrane excitability in the early stage of CIM.
CLINICAL NEUROPHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yukari Endo, Linda Groom, Sabrina M. Wang, Emanuela Pannia, Nigel W. Griffiths, Jenica L. M. Van Gennip, Brian Ciruna, Jocelyn Laporte, Robert T. Dirksen, James J. Dowling
Summary: CACNA1S-related myopathy is a congenital muscle disease with no effective therapies available. The lack of suitable animal models has hindered its study. Researchers have successfully generated zebrafish models that mimic key aspects of the severe and mild forms of the disease, providing a basis for future mechanistic studies and therapy development.
HUMAN MOLECULAR GENETICS
(2023)
Article
Multidisciplinary Sciences
Chien-Wen S. Kuo, Sara Dobi, Caglar Goek, Ana Da Silva Costa, Alice Main, Olivia Robertson-Gray, Daniel Baptista-Hon, Krzysztof J. Wypijewski, Hannah Costello, Tim G. Hales, Niall MacQuaide, Godfrey L. Smith, William Fuller
Summary: The α1C subunit of L-type Ca2+ channels, responsible for transmembrane Ca2+ fluxes, undergoes reversible palmitoylation in rat, rabbit, and human ventricular myocytes. The sites of palmitoylation are found in the N terminus and the linker between domains I and II of the channel. Unpalmitoylated α1C subunit leads to reduced voltage sensitivity of Ca2+ channels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Valerie Biancalana, John Rendu, Annabelle Chaussenot, Helen Mecili, Eric Bieth, Melanie Fradin, Sandra Mercier, Maud Michaud, Marie-Christine Nougues, Laurent Pasquier, Sabrina Sacconi, Norma B. Romero, Pascale Marcorelles, Francois Jerome Authier, Antoinette Gelot Bernabe, Emmanuelle Uro-Coste, Claude Cances, Bertrand Isidor, Armelle Magot, Marie-Christine Minot-Myhie, Yann Pereon, Julie Perrier-Boeswillwald, Gilles Bretaudeau, Nicolas Dondaine, Alison Bouzenard, Megane Pizzimenti, Bruno Eymard, Ana Ferreiro, Jocelyn Laporte, Julien Faure, Johann Bohm
Summary: The recurrent RYR1 mutation previously classified as VUS was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, providing evidence of its pathogenicity. This mutation causes an atypical congenital myopathy with slowly improving motor function over the first decades of life, indicating a potential for directing molecular diagnosis for patients with similar clinical presentation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Valentina Maria Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, Raquel Gomez-Oca, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xenia Massana Munoz, Nadege Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte
Summary: This study identifies BIN1 as a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations. By increasing BIN1 expression, muscle atrophy and histopathological features can be improved, and survival can be rescued.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Organic
Anastasiya Agafonova, Ilia A. Smetanin, Nikolai Rostovskii, Alexander F. Khlebnikov, Mikhail S. Novikov
Summary: This study presents a high-yield method for introducing a 2-pyridyl substituent in the C2 position of the three-membered ring of 2-bromo-2H-azirine-2-carboxylic acid derivatives through direct cross-coupling with 2-(trialkylstannyl)pyridines. The reaction is versatile, working well with different substituted 2-stannylpyridines and enabling the synthesis of 2-(thiazol-2-yl)-2H-azirines. DFT calculations suggest that the reaction proceeds through a sequence of S(N)2'-substitution, 1,4-stannyl shift, and [2,3]-sigmatropic shift of the pyridine ring.
Article
Cell Biology
Karla G. Espinosa, Salma Geissah, Linda Groom, Jonathan Volpatti, Ian C. Scott, Robert T. Dirksen, Mo Zhao, James J. Dowling
Summary: This study reported a new zebrafish model, zebrafish speg-DKO, of centronuclear myopathy (CNM), and demonstrated its ability to accurately recapitulate multiple phenotypes associated with CNM. This model provides a potential platform for investigating disease mechanisms and evaluating potential therapies for CNM.
DISEASE MODELS & MECHANISMS
(2022)
Review
Physiology
Walter C. Thompson, Paul H. Goldspink
Summary: This review focuses on the crucial role of 14-3-3 proteins in regulating excitation-contraction coupling in muscle, highlighting the need for further investigation into their mechanistic actions in force generation.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Biology
Xueyong Wang, Murad Nawaz, Chris DuPont, Jessica H. Myers, Steve Ra Burke, Roger A. Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich
Summary: Excitation-contraction coupling is the process of converting electrical excitation of muscle into force generation. Depolarization of skeletal muscle can lead to failure of ECC, specifically the failure to generate calcium transients. Different AP properties, such as AP peak and AP integral, play important roles in different steps of ECC, including AP conduction and calcium release.
Article
Biochemistry & Molecular Biology
Cathrine Nordgaard, Anna Constance Vind, Amy Stonadge, Rasmus Kjobsted, Goda Snieckute, Pedro Antas, Melanie Blasius, Marie Sofie Reinert, Ana Martinez Del Val, Dorte Breinholdt Bekker-Jensen, Peter Haahr, Yekaterina A. Miroshnikova, Abdelghani Mazouzi, Sarah Falk, Emeline Perrier-Groult, Christopher Tiedje, Xiang Li, Jens Rithamer Jakobsen, Nicolas Oldenburg Jorgensen, Jorgen F. P. Wojtaszewski, Frederic Mallein-Gerin, Jesper Lovind Andersen, Cristian Pablo Pennisi, Christoffer Clemmensen, Moustapha Kassem, Abbas Jafari, Thijn Brummelkamp, Vivian S. W. Li, Sara A. Wickstrom, Jesper Velgaard Olsen, Gonzalo Blanco, Simon Bekker-Jensen
Summary: This study reveals the mechanisms by which muscle fibers sense mechanical load to activate p38 and JNK signaling. ZAK is able to recognize stress fibers in cells and Z-discs in muscle fibers under mechanical stress. ZAK deficiency leads to skeletal muscle defects and changes in myosin profile.
Review
Biology
Rikke Birkedal, Martin Laasmaa, Jelena Branovets, Marko Vendelin
Summary: The development of the heart involves an increase in structural density and energy transfer efficiency. However, this increased density may restrict overall ATP/ADP diffusion. Disruption of this modular design in failing hearts may compromise intracellular energy transfer.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Neurosciences
Tara C. Tassin, Barbara Barylko, Per Niklas Hedde, Yan Chen, Derk D. Binns, Nicholas G. James, Joachim D. Mueller, David M. Jameson, Ronald Taussig, Joseph P. Albanesi
Summary: Mutations in the DNM2 gene are associated with motor disorders affecting nerve and muscle, such as CMT and CNM; CMT and CNM mutations have distinct effects on DNM2 function, suggesting different pathogenic mechanisms and genetic overlap should be re-examined.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Grace K. Muller, Joy Song, Vivek Jani, Yuejin Wu, Ting Liu, William P. D. Jeffreys, Brian O'Rourke, Mark E. Anderson, David A. Kass
Summary: PDE1i enhances contractility by increasing Ca(v)1.2 conductance in a PKA-dependent manner, with lesser total [Ca2+](i) increase, and without significant changes in the phosphorylation of critical EC-coupling proteins.
CIRCULATION RESEARCH
(2021)
Article
Clinical Neurology
Stephen A. Goutman, Kai Guo, Masha G. Savelieff, Adam Patterson, Stacey A. Sakowski, Hani Habra, Alla Karnovsky, Junguk Hur, Eva L. Feldman
Summary: By performing untargeted metabolomics in two independent ALS cohorts, this study identifies recurring pathways that are altered in both cohorts. Many of the pathways are involved in lipid metabolism, including beta-oxidation intermediates and complex and signalling lipids, such as sphingolipids and diacylglycerols.
Article
Endocrinology & Metabolism
Kai Guo, Masha G. Savelieff, Amy E. Rumora, Fadhl M. Alakwaa, Brian C. Callaghan, Junguk Hur, Eva L. Feldman
Summary: This study aimed to identify the plasma metabolomics and lipidomics signature that underlies PN in individuals with average class 3 obesity. The analysis showed significant differences in metabolites and lipids between lean and obese individuals, regardless of PN status. Stratification by PN status within obese individuals revealed differences in specific metabolic and lipid pathways.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Public, Environmental & Occupational Health
Stephen A. Goutman, Jonathan Boss, Christopher Godwin, Bhramar Mukherjee, Eva L. Feldman, Stuart A. Batterman
Summary: Occupational exposure to particulate matter, volatile organic compounds, metals, pesticides, and combustion and diesel exhaust, as well as employment in production occupations, are associated with an increased risk of ALS.
INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
(2022)
Article
Biochemistry & Molecular Biology
Junguk Hur, Ximena Paez-Colasante, Claudia Figueroa-Romero, Ting-wen Lo, Sami J. Barmada, Michelle T. Paulsen, Mats Ljungman, Fadhl M. Alakwaa, Masha G. Savelieff, Stephen A. Goutman, Eva L. Feldman
Summary: This study analyzes the miRNA profiles in patients with amyotrophic lateral sclerosis (ALS) and identifies different miRNA levels in different ALS mutation types. The study also reveals pathways related to ALS and suggests potential targets for future research. These findings contribute to the early diagnosis of ALS.
HUMAN MOLECULAR GENETICS
(2022)
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Gayatri Iyer, Hani Habra, Masha G. Savelieff, Alla Karnovsky, Bhramar Mukherjee, Eva L. Feldman
Summary: This study found that ALS participants experienced weight loss in the 5 years before enrollment, and long-term decrease in BMI was associated with lower survival rates. Metabolomic profiles were also found to be associated with BMI trajectories. Replicating these findings in other cohorts is necessary.
Review
Endocrinology & Metabolism
Melissa A. Elafros, Brian C. Callaghan, Lesli E. Skolarus, Loretta Vileikyte, John G. Lawrenson, Eva L. Feldman
Summary: Knowledge about microvascular complications of diabetes varies among patients and healthcare providers, with factors such as education level, disease duration, and socioeconomic status influencing patient knowledge. Misconceptions regarding appropriate screening practices for complications are common among healthcare providers. Further research is needed to identify interventions that can improve knowledge and outcomes for both patients and providers.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Christopher Godwin, Bhramar Mukherjee, Eva L. Feldman, Stuart A. Batterman
Summary: This study aimed to investigate the associations between occupational settings, self-reported occupational exposures, and survival and onset segment of ALS. The findings suggest that work in production occupations, military occupations, and self-reported occupational pesticide exposure are associated with poorer survival. Furthermore, specific occupational settings and exposures are associated with different onset segments of ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Stephanie A. Eid, Mohamed Noureldein, Bhumsoo Kim, Lucy M. Hinder, Faye E. Mendelson, John M. Hayes, Junguk Hur, Eva L. Feldman
Summary: This study characterized the transcriptional profiles and intercellular communication of Schwann cells (SCs) in a mouse model of prediabetes and neuropathy. The results revealed that SCs can adapt to metabolic stress and inflammation by altering their intercellular communication, which influences the progression of nerve pathophysiology. This study provides important insights into the function and communication mechanisms of SCs in nerve pathology.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Neurosciences
Stephanie A. Eid, Amy E. Rumora, Bogdan Beirowski, David L. Bennett, Junguk Hur, Masha G. Savelieff, Eva L. Feldman
Summary: The prevalence of diabetes is increasing due to the aging population, with type 2 diabetes being the most common type. Diabetic peripheral neuropathy is a complication that damages peripheral nerves and is influenced by metabolic and bioenergetic dysfunction. Recent evidence suggests that obesity and dyslipidemia also contribute to this condition.
Article
Clinical Neurology
Ayse J. Muniz, Tugba Topal, Michael D. Brooks, Angela Sze, Do Hoon Kim, Jacob Jordahl, Joe Nguyen, Paul H. Krebsbach, Masha G. Savelieff, Eva L. Feldman, Joerg Lahann
Summary: In this study, scientists developed an engineered extracellular matrix (EECM) to provide support and cell-to-matrix interactions for developing brain organoids. Compared to conventional protein matrix, EECMs enhanced neurogenesis, glial maturation, and neuronal diversity. The EECMs also supported long-term culture and produced brain organoids with increased protein diversity.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Rosemary E. Henn, Kai Guo, Sarah E. Elzinga, Mohamed H. Noureldein, Faye E. Mendelson, John M. Hayes, Diana M. Rigan, Masha G. Savelieff, Junguk Hur, Eva L. Feldman
Summary: Obesity is a global concern associated with cognitive impairment. It induces brain inflammation and activates microglia, leading to synaptic spine phagocytosis and cognitive impairment. The mechanisms of microglial activation during obesity are not fully understood.
Article
Clinical Neurology
Stephen A. Goutman, Jonathan Boss, Dae-Gyu Jang, Bhramar Mukherjee, Rudy J. Richardson, Stuart Batterman, Eva L. Feldman
Summary: This study aimed to replicate previous findings regarding the association between persistent organic pollutants (POPs) and amyotrophic lateral sclerosis (ALS) risk and survival. The analysis of samples from 164 ALS patients and 105 control participants showed that several POPs were significantly associated with ALS risk, and the combined mixture of all POPs was associated with ALS survival.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Stephen A. Goutman, Masha G. Savelieff, Dae-Gyu Jang, Junguk Hur, Eva L. Feldman
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration, with both genetic and environmental factors contributing to the risk and rate of disease progression. Epidemiological studies suggest potential contributions to the ALS exposome from pesticides, occupational exposures, sports and physical activity, metals, air pollution, trauma, electromagnetic fields, the gut microbiome, diet and lifestyle factors. The mechanisms underlying the effects of environmental factors on ALS risk remain incompletely understood but might involve neurotoxicity from specific environmental toxins, microbiome-mediated changes, epigenetic restructuring, systemic and central inflammation, and excitotoxicity. Most studies of the ALS exposome have a retrospective design using questionnaires and are, therefore, prone to recall bias and other limitations. Future studies will require prospective, longitudinal designs that include quantification of exposures in biosamples in addition to questionnaires.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
In-Young Choi, Wen-Tung Wang, Bhumsoo Kim, Junguk Hur, David C. Robbins, Dae-Gyu Jang, Masha G. Savelieff, Eva L. Feldman, Phil Lee
Summary: This study characterized the metabolic changes in the brain of patients with T2D using in vivo H-1 magnetic resonance spectroscopy. Elevated levels of several metabolites were observed in both T2D patients and T2D mice, indicating the impact of poorly controlled hyperglycemia on brain metabolism. The study demonstrates the utility of H-1 magnetic resonance spectroscopy in monitoring and understanding the metabolic changes in T2D progression.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Clinical Neurology
Melissa A. Elafros, Henning Andersen, David L. Bennett, Masha G. Savelieff, Vijay Viswanathan, Brian C. Callaghan, Eva L. Feldman
Summary: Diabetic peripheral neuropathy is a common complication of diabetes, and early diagnosis and treatment are crucial for improving patients' quality of life. Hyperglycemia and metabolic syndrome are major risk factors for the development of diabetic peripheral neuropathy.
