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)
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
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.
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)
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
Natalia N. Singh, Shaine Hoffman, Prabhakara P. Reddi, Ravindra N. Singh
Summary: Spinal muscular atrophy (SMA) is a major genetic disorder associated with infant mortality, primarily caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The spectrum of SMA ranges from prenatal death to survival into adulthood, with all tissues potentially affected.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(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
Neurosciences
Kaitlyn M. Kray, Vicki L. McGovern, Deepti Chugh, W. David Arnold, Arthur H. M. Burghes
Summary: Spinal muscular atrophy (SMA) is a genetic disease characterized by SMN protein deficiency leading to motor neuron loss and muscle atrophy. Increasing SMN levels before symptom onset provides the greatest therapeutic benefit, but treatment after motor neuron loss has occurred also shows effectiveness.
NEUROBIOLOGY OF DISEASE
(2021)
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)
Article
Biochemistry & Molecular Biology
Eric William Ottesen, Diou Luo, Natalia Nikolaevna Singh, Ravindra Narayan Singh
Summary: The intronic splicing silencer N1 (ISS-N1) within Survival Motor Neuron 2 (SMN2) intron 7 is a therapeutic target for treating spinal muscular atrophy. Treatment with 100 nM of Anti-N1 resulted in substantial stimulation of SMN2 exon 7 inclusion but also caused significant perturbations in the transcriptome and widespread aberrant splicing. Shorter ISS-N1-targeting ASOs showed a substantial reduction in off-target effects, providing important insights for better ASO design and dosing regimens of ASO-based drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Inge Schwersenz, Maggie C. Walter, Matthias Baumann, Manuela Baumgartner, Marcus Deschauer, Astrid Eisenkoelbl, Marina Flotats-Bastardas, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Koehler, Heike Koelbel, Monika Mueller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stoegmann, Regina Trollmann, Katharina Vill, Claudia Weiss, Gert Wiegand, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study presents real-world evidence on the effects of nusinersen treatment in patients with early-onset spinal muscular atrophy. The findings demonstrate significant improvements in motor function, particularly in children under the age of 2. However, the improvements in bulbar and respiratory function are not equivalent to those in motor function.
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
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
Zoology
Jeremy Tissier, Jean-Claude Rage, Renaud Boistel, Vincent Fernandez, Nicolas Pollet, Geraldine Garcia, Michel Laurin
ZOOLOGICAL JOURNAL OF THE LINNEAN SOCIETY
(2016)
Article
Genetics & Heredity
Lena Vouillot, Aurore Thelie, Nicolas Pollet
G3-GENES GENOMES GENETICS
(2015)
Review
Immunology
Bruno M. Colombo, Thibault Scalvenzi, Sarah Benlamara, Nicolas Pollet
FRONTIERS IN IMMUNOLOGY
(2015)
Article
Cell Biology
Odile J. Bronchain, Albert Chesneau, Anne-Helene Monsoro-Burq, Pascale Jolivet, Elodie Paillard, Thomas S. Scanlan, Barbara A. Demeneix, Laurent M. Sachs, Nicolas Pollet
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2017)
Article
Multidisciplinary Sciences
Santosh Kumar Maharana, Nicolas Pollet, Gerhard Schlosser
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Marion Bougerol, Frederic Aurade, Francois M. Lambert, Didier Le Ray, Denis Combes, Muriel Thoby-Brisson, Frederic Relaix, Nicolas Pollet, Herve Tostivint
Article
Biochemistry & Molecular Biology
Naoji Yubuki, Luis Javier Galindo, Guillaume Reboul, Purificacion Lopez-Garcia, Matthew W. Brown, Nicolas Pollet, David Moreira
MOLECULAR BIOLOGY AND EVOLUTION
(2020)
Article
Genetics & Heredity
Michelle Louise Zattera, Camilla Borges Gazolla, Amanda de Araujo Soares, Thiago Gazoni, Nicolas Pollet, Shirlei Maria Recco-Pimentel, Daniel Pacheco Bruschi
FRONTIERS IN GENETICS
(2020)
Article
Biotechnology & Applied Microbiology
Valerie Ducret, Adam J. Richards, Mathieu Videlier, Thibault Scalvenzi, Karen A. Moore, Konrad Paszkiewicz, Camille Bonneaud, Nicolas Pollet, Anthony Herrel
Summary: The study identified significant differential gene expression related to burst performance and endurance in Xenopus allofraseri, involving pathways such as actin filament polymerization, ATPase activity, cellular trafficking, and mitochondrial activity. Transcript isoforms of key genes and up-regulation of myosin-binding protein C fast-type were also observed, indicating potential mechanisms underlying locomotor performance trade-offs. These results suggest a role for calcium signaling, endoplasmic reticulum stress responses, alternative splicing, and cellular activity in the evolution of locomotor performance trade-offs.
Article
Genetics & Heredity
Heloise Muller, David Ogereau, Jean-Luc Da Lage, Claire Capdevielle, Nicolas Pollet, Taiadjana Fortuna, Remi Jeannette, Laure Kaiser, Clement Gilbert
Summary: This study reports the assembly of the nuclear and mitochondrial genome of the Mediterranean corn borer, providing insights into genome characteristics and genes related to sex determination. Additionally, detailed annotation of protein-coding genes was provided, laying a solid molecular foundation for studying insect genome evolution and the development of biocontrol strategies.
G3-GENES GENOMES GENETICS
(2021)
Article
Multidisciplinary Sciences
Teo Hebra, Nicolas Pollet, David Touboul, Veronique Eparvier
Summary: This study explored the metabolites of termite mutualistic strains from French Guiana using metabolomic analysis and whole genome sequencing. Two families of chlorinated polyketides were identified, and the biosynthetic pathways related to these compounds were defined. New halogenated metabolites were synthesized by exploiting the enzymatic promiscuity.
SCIENTIFIC REPORTS
(2022)
Article
Ecology
J. Guilliet, G. Baudouin, N. Pollet, J. Filee
Summary: Our study analyzed a large dataset of complete mitochondrial genomes of the Black Soldier Fly (BSF) to understand its evolution and timing. We discovered worldwide genetic diversity in the BSF, with 52 haplotypes found across five continents. Phylogenetic analysis of 60 complete mitochondrial genomes resolved the major BSF haplotypes and estimated separation events to more than 2 million years ago. Our data confirm that the North American lineage gave birth to commercial BSF stocks that spread globally through farm escapements. The study highlights the low genetic diversity of commercial BSF stocks and calls for further research to understand their specific adaptations for industrial needs.
BMC ECOLOGY AND EVOLUTION
(2022)
Article
Biotechnology & Applied Microbiology
Sophie Dhorne-Pollet, Eric Barrey, Nicolas Pollet
Article
Developmental Biology
P. Spirhanzlova, S. Dhorne-Pollet, J. S. Fellah, C. Da Silva, T. Tlapakova, K. Labadie, J. Weissenbach, J. Poulain, T. Jaffredo, P. Wincker, V. Krylov, N. Pollet
DEVELOPMENTAL BIOLOGY
(2017)
Meeting Abstract
Biochemistry & Molecular Biology
Thiago Gazoni, Jorge Pereira, Jorge Pereira, Nicolas Pollet, Patricia Parise-Maltempi, Malcom Ferguson-Smith
CHROMOSOME RESEARCH
(2015)