Article
Neurosciences
Didu S. T. Kariyawasam, Arlene M. D'Silva, Karen Herbert, James Howells, Kate Carey, Tejaswi Kandula, Michelle A. Farrar, Cindy (Shin-Yi) Lin
Summary: The study found significant axonal changes in children with spinal muscular atrophy, especially in early childhood. Treatment with nusinersen can restore the developmental trajectory of motor axons and reduce neurodegeneration.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Neurosciences
Kristine S. Ojala, Emily J. Reedich, Christine J. DiDonato, Stephen D. Meriney
Summary: Spinal muscular atrophy (SMA) was previously considered a devastating neuromuscular disease with poor prognosis, but recent advancements in genetically targeted therapies have transformed it into a prototype for monogenic disease treatment, significantly improving quality of life and survival rates for affected individuals.
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
Chemistry, Analytical
Zhiqing Hu, Miaomiao Chen, Chunhua Zhang, Zhuo Li, Mai Feng, Lingqian Wu, Miaojin Zhou, Desheng Liang
Summary: Spinal muscular atrophy (SMA) is a major genetic cause of infant death. Researchers have developed a novel nucleic acid diagnostic method combining CRISPR/Cas14a1 and asymmetric PCR, which can specifically and sensitively detect the deletion of exon 7 of the SMN1 gene in SMA patients. The method has been validated in clinical samples and showed consistent results with other detection methods, demonstrating its potential as an accurate detection platform for genetic diseases and pathogens.
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)
Article
Biochemistry & Molecular Biology
Andra V. Krauze, Yingdong Zhao, Ming-Chung Li, Joanna Shih, Will Jiang, Erdal Tasci, Theresa Cooley Zgela, Mary Sproull, Megan Mackey, Uma Shankavaram, Philip Tofilon, Kevin Camphausen
Summary: The addition of VPA to standard CRT treatment for GBM leads to differential alterations in proteomic expression pre- vs. post-completion of concurrent chemoirradiation, potentially influencing patient outcomes. The identified protein signals and hallmark gene sets associated with VPA treatment align with known biological pathways, providing insight into the mechanisms of action and potential biomarkers for future studies.
Article
Clinical Neurology
Nadja Ratia, Edouard Palu, Hanna Lantto, Emil Ylikallio, Ritva Luukkonen, Anu Suomalainen, Mari Auranen, Paivi Piirila
Summary: In cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.
FRONTIERS IN NEUROLOGY
(2023)
Review
Neurosciences
Brunhilde Wirth
Summary: The review highlights the challenging journey from gene discovery to therapy in spinal muscular atrophy (SMA), emphasizing the importance of perseverance in uncovering the biological mechanisms of the disease. Despite the impressive improvements seen with three therapeutic strategies in SMA, there are still many unanswered questions that need to be addressed as discussed in the review.
TRENDS IN NEUROSCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Marie Kuehne, Henry Lindemann, Christian Grune, Daniel Schroeder, Zoltan Cseresnyes, Maren Godmann, Andreas Koschella, Marc Thilo Figge, Christian Eggeling, Dagmar Fischer, Thomas Heinze, Thorsten Heinzel
Summary: Bio-based nanoparticles (NPs) as drug carriers have rapid cellular uptake, no cytotoxicity, and ability to induce histone H3 hyperacetylation, making them suitable for treating inflammation, sepsis, and cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Pharmacology & Pharmacy
Sai Teja Meka, Sree Lalitha Bojja, Gautam Kumar, Sumit Raosaheb Birangal, Mallikarjuna Rao
Summary: Parkinson's Disease (PD) is a rapidly growing neurological disorder with high disability and mortality rates. Current treatments focus on symptomatic relief but there is a need for disease-modifying therapies. Recent research has identified histone deacetylase inhibitors (HDACi) as potential drug targets for neurodegenerative diseases like PD. A study found that a novel pan-HDACi showed neuroprotective effects in a PD rat model by reducing oxidative stress and inflammation, and restoring dopamine levels in the striatum.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Audrey M. Winkelsas, Christopher Grunseich, George G. Harmison, Katarzyna Chwalenia, Carlo Rinaldi, Suzan M. Hammond, Kory Johnson, Melissa Bowerman, Sukrat Arya, Kevin Talbot, Matthew J. Wood, Kenneth H. Fischbeck
Summary: Research shows that ASOs targeting the 50 end of SMN2 can increase SMN mRNA and protein levels by inhibiting SMN2 mRNA decay. Combining 50 UTR ASO with SSO can elevate SMN levels beyond those achieved with SSO alone, offering a new therapeutic target for SMA.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
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)
Review
Genetics & Heredity
Jan Lejman, Grzegorz Zielinski, Piotr Gawda, Monika Lejman
Summary: Alternative splicing is a crucial mechanism that increases genetic diversity and can be a therapeutic target. Spinal Muscular Atrophy (SMA) is a neurodegenerative disease mainly caused by the homozygous deletion in the SMN1 gene, with 95% of cases attributed to this mutation.
Article
Clinical Neurology
Laura E. Habets, Bart Bartels, Fay-Lynn Asselman, Melissa T. Hooijmans, Sandra van den Berg, Aart J. Nederveen, W. Ludo van der Pol, Jeroen A. L. Jeneson
Summary: This study provides clinical evidence of abnormal muscle bioenergetics in patients with hereditary proximal spinal muscular atrophy, suggesting a potential role of mitochondrial dysfunction in the disease pathogenesis. The study also highlights the contribution of degeneration and atrophy of motor neurons and associated musculature, as well as the depletion of specific myofiber types, to muscle weakness in this cohort. These findings contribute to a better understanding of the underlying mechanisms of the disease and provide potential new biomarkers and targets for therapy.
Review
Cell Biology
Linda Bieniussa, Ipsa Jain, Montserrat Bosch Grau, Lukas Juergens, Rudolf Hagen, Carsten Janke, Kristen Rak
Summary: The organ of Corti in the inner ear is responsible for converting auditory signals into neuronal action potentials for processing by the brain. While the role of actin in hearing has been well-studied, this article highlights the importance of microtubules and their regulating mechanisms in the cochlea's function and their implications for hearing research.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Otorhinolaryngology
Franz-Tassilo Muller-Graff, Johannes Voelker, Anja Kurz, Rudolf Hagen, Tilmann Neun, Kristen Rak
Summary: The preoperative prediction of electrode position in cochlear implantation can be accurately done using otological planning software and different clinical imaging modalities. High-resolution imaging, such as fpVCT(SECO), is recommended for more accurate predictions.
COCHLEAR IMPLANTS INTERNATIONAL
(2023)
Article
Clinical Neurology
Francesca De Lorenzo, Patrick Luningschror, Jinhan Nam, Liam Beckett, Federica Pilotto, Emilia Galli, Paivi Lindholm, Cora Rudt von Collenberg, Simon Tii Mungwa, Sibylle Jablonka, Julia Kauder, Nadine Thau-Habermann, Susanne Petri, Dan Lindholm, Smita Saxena, Michael Sendtner, Mart Saarma, Merja H. Voutilainen
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons and has no cure or effective therapy. This study investigates the therapeutic effect of cerebral dopamine neurotrophic factor in rodent models of ALS and shows that it significantly halts disease progression and improves motor behavior. Cerebral dopamine neurotrophic factor rescues motor neurons from endoplasmic reticulum stress-related cell death and enhances motor neuron survival.
Article
Clinical Neurology
Kristen Rak, Carolina Koestler, Ute Geiger, Stefan Kaulitz, David Herrmann, Wafaa Shehata-Dieler, Rudolf Hagen, Mario Cebulla
Summary: The objective of this study was to investigate the benefit of intraoperative auditory brainstem response (ABR) measurements in revision active middle ear implant surgery. Results showed that the application of ABR measurement improved sound field thresholds and enhanced speech understanding. Analysis revealed a significant correlation between intraoperative gain in ABR threshold and postoperative gain in sound field thresholds. Therefore, ABR monitoring can be a useful tool to improve postoperative hearing success, especially in revision surgeries.
OTOLOGY & NEUROTOLOGY
(2023)
Article
Cell Biology
Thomas Andreska, Patrick Luningschror, Daniel Wolf, Rhonda L. McFleder, Maurilyn Ayon-Olivas, Marta Rattka, Christine Drechsler, Veronika Perschin, Robert Blum, Sarah Aufmkolk, Noelia Granado, Rosario Moratalla, Markus Sauer, Camelia Monoranu, Jens Volkmann, Chi Wang Ip, Christian Stigloher, Michael Sendtner
Summary: Parkinson's disease (PD) is characterized by impaired motor control. Cortico-striatal synapses, along with brain-derived neurotrophic factor (BDNF) and TrkB, play crucial roles in motor learning. Dopamine depletion in PD reduces the responsiveness of striatal medium spiny projection neurons (SPNs) to BDNF, leading to impaired TrkB processing and disturbed motor function. Sortilin related VPS10 domain containing receptor 2 (SORCS-2) may protect intracellular TrkB clusters from lysosomal degradation.
Article
Cell Biology
Bita Massih, Alexander Veh, Maren Schenke, Simon Mungwa, Bettina Seeger, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Peter Reinhardt, Jared Sterneckert, Andreas Hermann, Michael Sendtner, Patrick Lueningschroer
Summary: This article introduces a human neuromuscular co-culture system that enables the formation of neuromuscular junctions by differentiating induced pluripotent stem cells into motor neurons and 3D skeletal muscle tissue. The system is suitable for modeling the pathophysiology of motor neuron diseases and has been used to study the synaptic coupling and muscle contraction in Amyotrophic Lateral Sclerosis (ALS). This in vitro model recapitulates aspects of human physiology and is of great importance for studying human motor neurons in health and disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Health Care Sciences & Services
Georg Mathias Sprinzl, Astrid Magele, Philipp Schoerg, Rudolf Hagen, Kristen Rak, Anja Kurz, Paul Van de Heyning, Miryam Calvino, Luis Lassaletta, Javier Gavilan
Summary: This study aims to evaluate the overall benefits of hearing rehabilitation by presenting both audiological and subjective outcomes in one graph using data from an existing study. The graph allows tracking the user's performance over time and visualizing the correlation between different measures.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biology
Jonas Engert, Bjoern Spahn, Linda Bieniussa, Rudolf Hagen, Kristen Rak, Johannes Voelker
Summary: This study aimed to investigate the neural stem cell potential of the medial geniculate body (MGB). The findings showed that MGB cells exhibited the cardinal features of neural stem cells, including self-renewal, formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings contribute to a better understanding of the development of the auditory pathway.
Article
Clinical Neurology
Cordula Matthies, Laura Zeller, Anja Kurz, Kristen Rak, Rudolf Hagen, Wafaa Shehata-Dieler
Summary: This study provides a new EABR Classification Scheme for ABI surgery based on the analysis of EABR data. The findings show that all 23 subjects had EABR at the final ABI position and experienced auditory sensations at first activation. The most common EABR morphology consisted of two peaks, Classes B and C.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Cell Biology
Patrick Lueningschroer, Thomas Andreska, Alexander Veh, Daniel Wolf, Neha Jadhav Giridhar, Mehri Moradi, Angela Denzel, Michael Sendtner
Summary: The interaction between Calnexin and Fam134b plays a crucial role in targeting TrkB to the cell surface or autophagosomes, regulating the sensitivity of neurons to BDNF.
DEVELOPMENTAL CELL
(2023)
Article
Multidisciplinary Sciences
Saeede Salehi, Abdolhossein Zare, Gianluca Prezza, Jakob Bader, Cornelius Schneider, Utz Fischer, Felix Meissner, Matthias Mann, Michael Briese, Michael Sendtner
Summary: The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Here, the authors reveal an additional role of cytosolic Ptbp2, which regulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein hnRNP R.
NATURE COMMUNICATIONS
(2023)
Article
Health Care Sciences & Services
Anja Kurz, David Herrmann, Rudolf Hagen, Kristen Rak
Summary: Anatomy-based fitting (ABF) maps are potentially more effective than conventional clinically based fitting (CBF) methods for cochlear implant (CI) users. ABF maps were created using information from exact electrode contact positions determined by high-resolution computer tomography and clinical fitting software. In a study involving 10 bilateral CI users, the ABF map provided better speech understanding in quiet and noisy environments compared to the CBF map. Participants were more likely to accept the ABF map if their electrode array stimulated the apical region of their cochlea. The self-perceived sound quality with the ABF map was similar to the CBF map. ABF mapping may be an effective tool to compensate for frequency-to-place mismatch in experienced bilateral CI users.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biology
Maurilyn Ayon-Olivas, Daniel Wolf, Thomas Andreska, Noelia Granado, Patrick Lueningschroer, Chi Wang Ip, Rosario Moratalla, Michael Sendtner
Summary: Motor dysfunction in Parkinson's disease is linked to the depletion of dopamine and altered synaptic plasticity in striatal neurons. Stimulation of dopamine receptor D1 enhances synaptic plasticity in direct pathway spiny projection neurons, while stimulation of dopamine receptor D2 inhibits synaptic plasticity in indirect pathway spiny projection neurons. This study demonstrates the role of tropomyosin receptor kinase B (TrkB) and brain-derived neurotrophic factor (BDNF) in regulating synaptic plasticity at corticostriatal synapses. Dysregulated BDNF/TrkB signaling may contribute to the pathophysiology of both direct and indirect pathway striatal projection neurons in Parkinson's disease.
Article
Biology
Jonas Engert, Julia Doll, Barbara Vona, Totta Ehret Kasemo, Bjoern Spahn, Rudolf Hagen, Kristen Rak, Johannes Voelker
Summary: This study investigated the changes in mRNA abundance of genes influencing neural stem cell development and neurogenesis in the rat cochlear nucleus over time. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected. Crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. These findings contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway.
Article
Cell Biology
Karri Kaivola, Ruth Chia, Jinhui Ding, Memoona Rasheed, Masashi Fujita, Vilas Menon, Ronald L. Walton, Ryan L. Collins, Kimberley Billingsley, Harrison Brand, Michael Talkowski, Xuefang Zhao, Ramita Dewan, Ali Stark, Anindita Ray, Sultana Solaiman, Pilar Alvarez Jerez, Laksh Malik, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Mario Maselis, Julia Keith, Eric Int LBD Genomics Consortium, Ali Int ALS FTD Consortium, Pentti PROSPECT Consortium, Toshiko Tanaka, Eric Topol, Ali Torkamani, Pentti Tienari, Tatiana M. Foroud, Bernardino Ghetti, John E. Landers, Mina Rtyen, Huw R. Morris, John A. Hardy, Letizia Mazzini, Sandra D'Alfonso, Cristina Moglia, Andrea Calvo, Geidy E. Serrano, Thomas G. Beach, Tanis Ferman, Neill R. Graff-Radford, Bradley F. Boeve, Zbigniew K. Wszolek, Dennis W. Dickson, Adriano Chio, David A. Bennett, Philip L. De Jager, Owen A. Ross, Clifton L. Dalgard, J. Raphael Gibbs, Bryan J. Traynor, Sonja W. Scholz
Summary: This study characterized the role of structural variants in Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). The researchers discovered a novel risk locus for LBD and found associations between known structural variants and FTD/ALS. Rare pathogenic structural variants were also identified in both LBD and FTD/ALS. The study provides a catalog of structural variants for further understanding of the pathogenesis of these forms of dementia.
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)
