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
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
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
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
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
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
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.
Review
Biochemistry & Molecular Biology
Hisahide Nishio, Emma Tabe Eko Niba, Toshio Saito, Kentaro Okamoto, Yasuhiro Takeshima, Hiroyuki Awano
Summary: Spinal muscular atrophy (SMA) is an autosomal recessive lower motor neuron disease. The genetic homogeneity of SMA was proved in 1990, five years after the identification of the responsible gene, SMN1. Genetic testing has revealed that SMA occurs in 1 of 10,000 to 20,000 live births and more than 95% of affected patients have SMN1 deletion. Nusinersen, onasemnogene abeparvovec, and risdiplam have been approved for SMA treatment, and clinical trials have shown that pre-symptomatic SMA patients can achieve developmental milestones with these drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Tejal Aslesh, Toshifumi Yokota
Summary: Spinal muscular atrophy (SMA) is a common genetic neurodegenerative disorder characterized by progressive muscle weakness. The disease is caused by the loss or mutation of the SMN1 gene, with the severity inversely correlated with the number of SMN2 gene copies. Current FDA-approved treatment strategies for SMA aim to increase functional SMN production from the SMN2 gene. Additionally, gene replacement therapy using Onasemnogene abeparvovec has also been approved.
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
Clinical Neurology
Domenico D'Amico, Olivier Biondi, Camille Januel, Cynthia Bezier, Delphine Sapaly, Zoe Clerc, Mirella El Khoury, Venkat Krishnan Sundaram, Leo Houdebine, Thibaut Josse, Bruno Della Gaspera, Cecile Martinat, Charbel Massaad, Laure Weill, Frederic Charbonnier
Summary: This study reveals that the IRE1 alpha/XBP1 branch of the unfolded protein response is disrupted in spinal muscular atrophy (SMA), with a depletion of XBP1s contributing to SMA pathogenesis. Rebalancing XBP1s expression can induce SMN expression and protect spinal motor neurons in severe SMA-like mice.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Francesco Errico, Carmen Marino, Manuela Grimaldi, Tommaso Nuzzo, Valentina Bassareo, Valeria Valsecchi, Chiara Panicucci, Elia Di Schiavi, Tommaso Mazza, Claudio Bruno, Adele D'Amico, Manolo Carta, Anna Maria D'Ursi, Enrico Bertini, Livio Pellizzoni, Alessandro Usiello
Summary: In this study, the metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of spinal muscular atrophy (SMA) patients were characterized using nuclear magnetic resonance (NMR) spectroscopy. The results showed that Nusinersen can modulate amino acid metabolism with distinct downstream metabolic effects according to disease severity. These findings suggest that Nusinersen selectively modulates peripheral organ metabolism in severe SMA patients.
Article
Clinical Neurology
Crystal M. Proud, Eugenio Mercuri, Richard S. Finkel, Janbernd Kirschner, Darryl C. De Vivo, Francesco Muntoni, Kayoko Saito, Eduardo F. Tizzano, Isabelle Desguerre, Susana Quijano-Roy, Kamal Benguerba, Dheeraj Raju, Eric Faulkner, Laurent Servais
Summary: This study aimed to devise a rational and systematic approach for defining and grouping disease-modifying treatment scenarios for survival motor neuron-targeted diseases. The proposed classification, based on initial and subsequent treatment differentiation, was validated by applying it to the patients in the RESTORE registry.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Cell Biology
Angela Koh, Menachem Viktor Sarusie, Jurgen Ohmer, Utz Fischer, Christoph Winkler, Thorsten Wohland
Summary: The research found that a decrease in SMN protein levels in patients with Spinal Muscular Atrophy may lead to transcript splicing defects, rather than active transport in axons; SMN acts as a chaperone for the assembly of snRNP and mRNP complexes in motor neurons, playing an important role.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natalia N. Singh, Collin A. O'Leary, Taylor Eich, Walter N. Moss, Ravindra N. Singh
Summary: This article reviews the structural context of exonic and intronic cis-elements that promote or prevent exon 7 recognition in SMN genes. It discusses how structural rearrangements triggered by single nucleotide substitutions can bring drastic changes in SMN2 exon 7 splicing. Potential mechanisms by which inter-intronic structures might impact splicing outcomes are also proposed.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
