Article
Clinical Neurology
Chaoping Hu, Xihua Li, Yiyun Shi, Xiaomei Zhu, Lei Zhao, Wenhui Li, Shuizhen Zhou, Yi Wang
Summary: This study provides insight into the comprehensive management and profile of different types of SMA patients in China, highlighting the importance of higher SMN2 copies for better survival and ambulation preservation. Patients receiving regular rehabilitation may have better joint function preservation.
FRONTIERS IN NEUROLOGY
(2022)
Review
Neurosciences
Giulietta M. M. Riboldi, Irene Faravelli, Paola Rinchetti, Francesco Lotti
Summary: Since its identification as the gene responsible for SMA, the functions of the SMN protein have expanded to include roles in RNA processing pathways, mRNA trafficking and translation, axonal transport, endocytosis, and mitochondria metabolism. The SMN complex's activities are regulated by various processes, with post-translational modifications (PTMs) emerging as important regulators. PTMs, such as phosphorylation, methylation, ubiquitination, acetylation, and sumoylation, modulate the pleiotropic functions of the SMN complex. This overview focuses on the PTMs involved in regulating the SMN complex and their implications in SMA pathogenesis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
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
Biochemistry & Molecular Biology
Rachel James, Helena Chaytow, Leire M. Ledahawsky, Thomas H. Gillingwater
Summary: SMA is an autosomal recessive motor neuron disease caused by mutations in the SMN1 gene. The development of combinatorial therapies for SMA is necessary, with mitochondria being a relevant target for such therapies. Understanding mitochondrial dysfunction in SMA may lead to the development of targeted mitochondrial therapies with potential benefits for other motor neuron diseases and neurodegenerative disorders.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Mar Costa-Roger, Laura Blasco-Perez, Ivon Cusco, Eduardo F. Tizzano
Summary: Comprehensive study of the SMN1 and SMN2 genes is crucial for better prediction of SMA in positive neonatal screening cases and early diagnosis to start treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Raffaella Adami, Daniele Bottai
Summary: Studying neural stem cells (NSCs) from spinal muscular atrophy (SMA) patients is important for identifying new treatment targets and supporting affected patients. However, studying NSCs in living patients is challenging, but can be done using animal models or induced pluripotent stem cells. Therapeutic interventions like NSCs transplantation could improve SMA condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pediatrics
John W. Day, Kelly Howell, Amy Place, Kimberly Long, Jose Rossello, Nathalie Kertesz, George Nomikos
Summary: Spinal muscular atrophy (SMA) is a genetic neuromuscular condition that affects spinal motor neurons. Current treatments have provided incremental improvements, but there is still a significant disease burden for many patients. The development of a combination therapy targeting myostatin inhibition shows potential for managing SMA.
Review
Medicine, General & Internal
Marija Babic, Maria Banovic, Ivana Berecic, Tea Banic, Mirjana Babic Leko, Monika Ulamec, Alisa Junakovic, Janja Kopic, Jadranka Sertic, Nina Barisic, Goran Simic
Summary: Spinal muscular atrophy (SMA) is a rare genetic disorder caused by the deletion or mutation of the SMN1 gene. Nusinersen and risdiplam, the first FDA-approved medications, increase the production of SMN protein from the backup SMN2 gene. The search for prognostic and pharmacodynamic biomarkers in SMA patients' body fluids is ongoing, although more research is needed to identify new biomarkers or combinations of biomarkers.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Neurosciences
Alba Sansa, Sandra de la Fuente, Joan X. Comella, Ana Garcera, Rosa M. Soler
Summary: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder caused by loss of the Survival Motor Neuron 1 gene (SMN1), leading to degeneration of spinal cord motoneurons and progressive muscular atrophy. The activation of apoptosis in SMA MNs and reduction of Akt phosphorylation may play a crucial role in regulating cell degeneration. Our observations suggest potential mechanisms for controlling cell loss in SMA.
NEUROBIOLOGY OF DISEASE
(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.
Review
Clinical Neurology
Nassim Rad, Haibi Cai, Michael D. Weiss
Summary: Spinal muscular atrophy (SMA) is a group of neurodegenerative disorders characterized by the loss of spinal motor neurons. The majority of patients have loss of expression of survival motor neuron (SMN) 1 protein due to the deletion or other mutations of the SMN1 gene, with the severity influenced by the copy numbers of the SMN2 gene. The management of adult SMA patients requires tailored treatment and multidisciplinary care. Emerging therapies like nusinersen and risdiplam show promise, but further study is needed to assess their efficacy in this population.
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
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)
Article
Neurosciences
Maria P. P. Miralles, Alba Sansa, Maria Beltran, Rosa M. M. Soler, Ana Garcera
Summary: Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by muscle weakness and degeneration of spinal cord motoneurons. In this study, the NF-kappa B pathway and Gemin3 protein were found to be reduced in SMA mouse and human motoneurons (MNs). Knockdown of Gemin3 resulted in decreased levels of SMN, IKK beta, and RelA proteins, as well as neurite degeneration in MNs.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Alba Sansa, Ivan Hidalgo, Maria P. Miralles, Sandra de la Fuente, M. Jose Perez-Garcia, Francina Munell, Rosa M. Soler, Ana Garcera
Summary: SMA is a genetic disease caused by reduced SMN protein, with unclear mechanisms in muscle. Studies show reduction of autophagy marker LC3-II in SMA muscle, while increased mTOR phosphorylation and LC3-II levels in SMA MNs. Opposite changes in autophagy proteins and mTOR phosphorylation between muscle cells and neurons suggest tissue-specific responses to therapies for SMA patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Melissa Bowerman, Lyndsay M. Murray, Frederique Scamps, Bernard L. Schneider, Rashmi Kothary, Cedric Raoul
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2018)
Review
Biochemistry & Molecular Biology
Matthew J. A. Wood, Kevin Talbot, Melissa Bowerman
HUMAN MOLECULAR GENETICS
(2017)
Article
Biochemistry & Molecular Biology
Lisa M. Walter, Christiane E. Koch, Corinne A. Betts, Nina Ahlskog, Katharina E. Meijboom, Tirsa L. E. van Westering, Gareth Hazell, Amarjit Bhomra, Peter Claus, Henrik Oster, Matthew J. A. Wood, Melissa Bowerman
HUMAN MOLECULAR GENETICS
(2018)
Article
Medicine, General & Internal
Lisa M. Walter, Marc-Olivier Deguise, Katharina E. Meijboom, Corinne A. Betts, Nina Ahlskog, Tirsa L. E. van Westering, Gareth Hazell, Emily McFall, Anna Kordala, Suzan M. Hammond, Frank Abendroth, Lyndsay M. Murray, Hannah K. Shorrock, Domenick A. Prosdocimo, Saptarsi M. Haldar, Mukesh K. Jain, Thomas H. Gillingwater, Peter Claus, Rashmi Kothary, Matthew J. A. Wood, Melissa Bowerman
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
Editorial Material
Neurosciences
Melissa Bowerman
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
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
Article
Clinical Neurology
Joseph M. Hoolachan, Emma R. Sutton, Melissa Bowerman
Article
Neurosciences
Darija Soltic, Melissa Bowerman, Joanne Stock, Hannah K. Shorrock, Thomas H. Gillingwater, Heidi R. Fuller
Review
Cell Biology
Melissa Bowerman, Catherina G. Becker, Rafael J. Yanez-Munoz, Ke Ning, Matthew J. A. Wood, Thomas H. Gillingwater, Kevin Talbot
DISEASE MODELS & MECHANISMS
(2017)