Article
Neurosciences
Emily J. Reedich, Martin Kalski, Nicholas Armijo, Gregory A. Cox, Christine J. DiDonato
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by genetic deficiency of the SMN protein. Studies have shown activation of the p53 and p21 pathways in SMA mice, but they are not primary drivers of motor neuron death in milder SMA mouse models like Smn(2B/-).
EXPERIMENTAL NEUROLOGY
(2021)
Review
Neurosciences
Jing Li, Xin Li, Liqun Wang, Guode Wu
Summary: This article reports a rare case of a 21-year-old female patient with co-existence of spinal muscular atrophy and moyamoya syndrome. After treatment, the patient's symptoms improved. However, further research is needed to elucidate the relationship between the two diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
V. A. Sansone, G. Coratti, M. C. Pera, M. Pane, S. Messina, F. Salmin, E. Albamonte, R. De Sanctis, M. Sframeli, V Di Bella, S. Morando, A. D'Amico, A. L. Frongia, L. Antonaci, A. Pirola, M. Pedemonte, E. Bertini, C. Bruno, E. Mercuri
Summary: The study compared demographics and disease characteristics between regularly followed SMA patients and newcomers, revealing differences in motor and respiratory function, particularly a higher proportion of newcomers at the severe end of the spectrum in type II patients. Only approximately a third of newcomers initiated treatment, compared to 51% of the regularly followed patients. Identification of patients not part of registries will help redefine the overall prevalence of SMA and different phenotypes.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Markus Leo, Linda-Isabell Schmitt, Michael Fleischer, Rebecca Steffen, Cora Osswald, Christoph Kleinschnitz, Tim Hagenacker
Summary: This study investigates the role of spinal astrocytes in the pathogenesis of late-onset SMA forms. Using a mouse model and SMA-like astrocytes, they observed the activation of spinal astrocytes, reduction of certain proteins, and impaired glutamate uptake and potassium uptake. These findings demonstrate the crucial role of spinal astrocytes in the development of late-onset SMA.
Article
Biochemistry & Molecular Biology
Laura Bianchi, Maria Sframeli, Lorenza Vantaggiato, Gian Luca Vita, Annamaria Ciranni, Francesca Polito, Rosaria Oteri, Eloisa Gitto, Fabrizio Di Giuseppe, Stefania Angelucci, Antonio Versaci, Sonia Messina, Giuseppe Vita, Luca Bini, M'hammed Aguennouz
Summary: Treatment with nusinersen in SMA type 1 patients led to a reversal trend of CSF protein profiles towards those of control donors, with significant up-regulation of apolipoprotein A1 and apolipoprotein E, as well as consistent changes in transthyretin proteoforms. These proteins play crucial roles in molecular processes aberrant in SMA, suggesting that they could serve as valuable biomarkers for assessing patient responsiveness and disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Marianna Maretina, Anna Egorova, Kristina Lanko, Vladislav Baranov, Anton Kiselev
Summary: This study tested three methods for measuring SMN transcript levels and compared several potential mRNA-based biomarkers in peripheral blood mononuclear cells of SMA patients, SMA carriers, and healthy individuals. The study found that the mean percentage of full-length SMN transcripts determined by semiquantitative and quantitative fluorescence RT-PCR differed significantly between the groups. The relevance of this biomarker was confirmed in a therapeutic experiment targeting the SMN2 gene.
Article
Cell Biology
Sharon J. Brown, Rachel A. Kline, Silvia A. Synowsky, Sally L. Shirran, Ian Holt, Kelly A. Sillence, Peter Claus, Brunhilde Wirth, Thomas M. Wishart, Heidi R. Fuller
Summary: This study conducted proteomic profiling of skin fibroblasts from different severities of spinal muscular atrophy (SMA) patients. The results showed limited overlap in differentially expressed proteomic profiles among different types of SMA, and the greatest variability was observed within SMA II fibroblasts. Despite limited proteomic overlap, common enriched canonical pathways were identified in two of the three SMA severities. The study also identified protein profiles that may be associated with SMA severity.
Article
Clinical Neurology
P. V. S. Souza, W. B. V. R. Pinto, A. Ricarte, B. M. L. Badia, D. D. Seneor, D. T. Teixeira, L. Caetano, E. A. Goncalves, M. A. T. Chieia, I. B. Farias, E. Bertini, A. S. B. Oliveira
Summary: This study identified a cohort of 20 patients with SMA type 4 in a Brazilian cohort of 227 SMA patients. The most common clinical symptom was limb-girdle muscle weakness, with absent tendon reflexes in 90% of patients and fasciculations in 45% of patients. The majority of patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 60% of them showing four copies of the SMN2 gene.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nora Tula Detering, Tobias Schuening, Niko Hensel, Peter Claus
Summary: Spinal muscular atrophy (SMA) is a disease caused by low levels of survival of motoneuron (SMN) protein. Phosphorylation of SMN is considered a key factor affecting SMN function in SMA. Phosphorylation can influence the localization, stability, and functions of SMN, making it a potential important target in SMA treatment strategies.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Marina Boido, Iacopo Gesmundo, Anna Caretto, Francesca Pedrolli, Roberta Schellino, Sheila Leone, Renzhi Cai, Wei Sha, Ezio Ghigo, Andrew V. Schally, Alessandro Vercelli, Riccarda Granata
Summary: The study shows that MR-409 has protective effects on SMN Delta 7 mice, indicating its potential as a promising drug for the treatment of SMA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Anton J. Blatnik, Vicki L. McGovern, Arthur H. M. Burghes
Summary: Proximal spinal muscular atrophy (SMA) is a genetic disorder characterized by motor neuron loss and skeletal muscle atrophy due to deficiency of the essential survival motor neuron (SMN) protein. Therapeutics aimed at increasing SMN protein levels have shown efficacy in treating SMA, but the mechanisms underlying motor neuron loss are still not well understood. Genetics and biochemistry have provided insights into SMA and SMN, from identifying genetic regions to developing potential treatments, but further research is needed to determine critical pathways in SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Diou Luo, Natalia Nikolaevna Singh, Ravindra Narayan Singh
Summary: This study investigates the generation mechanism of circRNA in SMN genes. It finds that the presence of introns enhances the rate of circRNA generation and that the exon junction complex plays a role in the generation of circRNAs containing only exons. In addition, SMN circRNAs are preferentially localized in the cytoplasm.
Article
Genetics & Heredity
M. A. Maretina, K. R. Valetdinova, N. A. Tsyganova, A. A. Egorova, V. S. Ovechkina, H. B. Schioth, S. M. Zakian, V. S. Baranov, A. Kiselev
Summary: The study found that certain genes in cells from spinal muscular atrophy patients have different methylation patterns compared to cells from healthy individuals, which helps deepen the understanding of the disease pathogenesis.
Article
Genetics & Heredity
Siiri Sarv, Tiina Kahre, Eve Vaidla, Sander Pajusalu, Kai Muru, Haide Poder, Katrin Gross-Paju, Sandra Utt, Riina Zordania, Inga Talvik, Eve Oiglane-Shlik, Kristina Muhu, Katrin Ounap
Summary: The study in Estonia described the birth prevalence of SMA from 1996 to 2020 and found that the birth prevalence of SMA in the country is similar to the median in Europe. The research provided valuable information on the epidemiology of SMA, which can guide the implementation of spinal muscular atrophy into the newborn screening program in Estonia.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Junjie Sun, Jiaying Qiu, Qiongxia Yang, Qianqian Ju, Ruobing Qu, Xu Wang, Liucheng Wu, Lingyan Xing
Summary: This study provides a single-cell atlas of the spinal cord in severe SMA mice, revealing different cell types and their differentially expressed genes. The communication between different cell types in the SMA spinal cord was significantly reduced. A subpopulation of vascular fibroblasts showed the most significant change, possibly leading to vascular defects and widespread protein synthesis and energy metabolism reductions in SMA mice.
Article
Biochemistry & Molecular Biology
Nina Ahlskog, Daniel Hayler, Anja Krueger, Sabrina Kubinski, Peter Claus, Suzan M. Hammond, Matthew J. A. Wood, Rafael J. Yanez-Munoz, Melissa Bowerman
Article
Neurosciences
Salim Benlefki, Ana Sanchez-Vicente, Vanessa Milla, Olivier Lucas, Claire Soulard, Richard Younes, Csilla Gergely, Melissa Bowerman, Cedric Raoul, Frederique Scamps, Cecile Hilaire
Article
Cell Biology
Samantha F. Kornfeld, Sarah E. Cummings, Samaneh Fathi, Sawyer R. Bonin, Rashmi Kothary
Summary: Research suggests that miR-145-5p plays a role in preventing differentiation and promoting proliferation in oligodendrocyte precursors and progenitor cells. This finding sheds light on the mechanisms of neurodevelopment.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Editorial Material
Neurosciences
Melissa Bowerman
Review
Neurosciences
Katherine S. Watson, Imane Boukhloufi, Melissa Bowerman, Simon H. Parson
Summary: Spinal muscular atrophy (SMA) is an autosomal recessive condition that typically presents in early infancy with progressive muscle weakness. Recent research has broadened the understanding of SMA beyond neuromuscular aspects, with a focus on fatty acid metabolism abnormalities. The potential of dietary interventions to modulate and reduce the adverse health effects in SMA patients is being explored.
Review
Biochemistry & Molecular Biology
Marc-Olivier Deguise, Lucia Chehade, Rashmi Kothary
Summary: Spinal muscular atrophy (SMA) is a genetic disorder causing paralysis, muscle atrophy, and death. Recent research suggests that gastrointestinal, metabolic, and endocrine defects may contribute to the disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Aoife Reilly, Lucia Chehade, Rashmi Kothary
Summary: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disease caused by the loss or deletion of the survival motor neuron 1 gene (SMN1). Significant advancements have been made in SMA therapeutics, improving the outcomes for patients. However, challenges and limitations still exist, necessitating further research for the best outcomes.
Article
Biochemistry & Molecular Biology
Aoife Reilly, Marc-Olivier Deguise, Ariane Beauvais, Rebecca Yaworski, Simon Thebault, Daniel R. Tessier, Vincent Tabard-Cossa, Niko Hensel, Bernard L. Schneider, Rashmi Kothary
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Current gene therapy and clinical trials for SMA have shown significant improvement in the clinical phenotype but not a complete cure. This study demonstrates the independent contribution of peripheral organs to SMA pathology and suggests that treatments should not be restricted to motor neurons.
Review
Biochemistry & Molecular Biology
Clarissa Ngo, Rashmi Kothary
Summary: Oligodendrocytes play a crucial role in the formation of myelin in the central nervous system. Demyelinating disorders like multiple sclerosis (MS) result in damaged myelin and slower transmission of electrical impulses. The failure of oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes hinders remyelination in MS. Understanding the regulation of oligodendrocyte development is important for developing new therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators of oligodendrocyte biology, influencing cell specification, proliferation, differentiation, and myelination. This article explores the role of miRNAs in oligodendrocyte biology and their potential as therapeutic tools for remyelination.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Neda A. M. Nafchi, Ellie M. M. Chilcott, Sharon Brown, Heidi R. R. Fuller, Melissa Bowerman, Rafael J. J. Yanez-Munoz
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in the survival motor neuron (SMN) 1 gene. A novel codon-optimized hSMN1 transgene was developed and lentiviral vectors with different promoters were tested for optimal expression. The integration-deficient lentiviral vectors showed high expression of the optimized transgene and are considered safer. Neonatal delivery of the optimized transgene using adeno-associated viral vectors resulted in a significant increase in SMN protein levels in SMA mouse models.
Article
Neurosciences
Diane S. Nakamura, Jean-David M. Gothie, Samantha F. Kornfeld, Rashmi Kothary, Timothy E. Kennedy
Summary: Oligodendrocytes produce lipid-rich myelin sheaths that support axonal function. Mitochondria in oligodendrocytes supply energy and carbon chains for lipid synthesis. The regulation of mitochondrial docking in oligodendrocytes is crucial for their proper distribution and function.
Article
Biochemistry & Molecular Biology
Sharon J. Brown, Darija Soltic, Silvia A. Synowsky, Sally L. Shirran, Ellie Chilcott, Hannah K. Shorrock, Thomas H. Gillingwater, Rafael J. Yanez-Munoz, Bernard Schneider, Melissa Bowerman, Heidi R. Fuller
Summary: Structural, functional and molecular cardiac defects have been found in SMA patients and mouse models. Proteomics analysis showed widespread molecular defects in severe SMA mice. This study investigated if similar changes can be found in less severe SMA mouse models, and found that many proteins related to cardiovascular development and function were dysregulated.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Jamuna Selvakumaran, Simona Ursu, Melissa Bowerman, Ngoc Lu-Nguyen, Matthew J. Wood, Alberto Malerba, Rafael J. Yanez-Munoz
Summary: The blood-brain barrier (BBB) is a specialized microvasculature system that protects the central nervous system (CNS) from toxic agents. Researchers have successfully differentiated induced pluripotent stem cells (iPSC) into brain microvascular endothelial cells (BMECs) to create a human BBB model. This model demonstrates tight barrier properties and can be used to evaluate drug penetration into the CNS.
Article
Cell Biology
Sebastian Rademacher, Nora T. Detering, Tobias Schuening, Robert Lindner, Pamela Santonicola, Inga-Maria Wefel, Janina Dehus, Lisa M. Walter, Hella Brinkmann, Agathe Niewienda, Katharina Janek, Miguel A. Varela, Melissa Bowerman, Elia Di Schiavi, Peter Claus
Review
Genetics & Heredity
Anisha Lynch-Godrei, Rashmi Kothary
NEUROLOGY-GENETICS
(2020)