Article
Multidisciplinary Sciences
Hideo Shimizu, Hirohiko Hohjoh
Summary: This study reveals that FMR1, FXR1, and Dlg4 genes associated with Fragile X syndrome are involved in the regulation of UPS activity and affect neurite outgrowth.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Andy Khamoui, Dorota Tokmina-Roszyk, Rafaela G. Feresin, Gregg B. Fields, Nishant P. Visavadiya
Summary: TMT-based quantitative proteomics was used to examine protein expression in skeletal muscle from mice with different severity of cancer cachexia. The study identified distinct mechanisms associated with cachexia severity and potential biomarkers and therapeutic targets.
Article
Biochemistry & Molecular Biology
Madison Edwards, Simpson Joseph
Summary: Fragile X Syndrome and certain manifestations of autism spectrum disorder are caused by improper RNA regulation due to a deficiency of fragile X mental retardation protein (FMRP). Fragile X related proteins (FXPs) play a crucial role in mRNA regulation and potential mRNA targets. This study investigated the function of FXPs in translational control using three potential mRNA targets, analyzing the binding site(s) of FXPs within the mRNA and their impact on translation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Jonathan Herring, Kirsten Johnson, Joerg Richstein
Summary: This article discusses the stigmatization, inaccuracy, and breadth of fragile X syndrome associated with the use of the term "retardation" in gene and protein naming. It proposes the adoption of a more inclusive terminology and suggests approaching the HGNC for new naming guidelines.
Article
Multidisciplinary Sciences
Dominic J. Vita, Cole J. Meier, Kendal Broadie
Summary: Glia play a crucial role in remodeling neural circuits during development. FMRP acts within neurons to activate glial insulin receptors, facilitating Draper- and Shrub-dependent neuronal clearance.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Chunzhu Song, Kendal Broadie
Summary: Drosophila models of neurological disease, particularly the FXS model, have greatly contributed to our understanding of the pathogenic mechanisms and neurological phenotypes of fragile X syndrome, and have provided potential therapeutic targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Obstetrics & Gynecology
C. Sonigo, A. Mayeur, M. Sadoun, M. Pinto, J. Benguigui, N. Frydman, S. Monnot, A. Benachi, J. Steffann, M. Grynberg
Summary: In females with FMR1 mutations or premutations undergoing preimplantation genetic testing (PGT), having seven or more mature oocytes in a cycle leads to an 83% chance of obtaining one or more healthy embryos. This study suggests that the number of mature oocytes is crucial in determining the success of transferring a healthy embryo in PGT cycles for FMR1 carriers.
HUMAN REPRODUCTION
(2021)
Article
Biochemical Research Methods
Mei-Mei Gao, Hang Shi, Hua-Juan Yan, Yue-Sheng Long
Summary: FMRP deficit is a common cause of FXS, which is characterized by intellectual disability and ASD. A proteomic analysis identified 100 differentially abundant proteins in the PFC of Fmr1 knockout mice, and bioinformatical analysis showed that these proteins were mainly enriched in the immune system, extracellular part, and complement and coagulation cascades.
JOURNAL OF PROTEOMICS
(2023)
Article
Cell Biology
Amanda St. Paul, Cali Corbett, Amanda Peluzzo, Sheri Kelemen, Rachael Okune, Dale S. Haines, Kyle Preston, Satoru Eguchi, Michael V. Autieri
Summary: This study identifies FXR1 as a key protein that connects cytoskeletal dynamics with mRNA stability. FXR1 binds to mRNA associated with cytoskeletal dynamics and depletion of FXR1 decreases their mRNA stability. FXR1 interacts with cytoskeletal proteins, particularly Arp2 and CYFIP1, and regulates actin polymerization. Depletion of FXR1 affects various cytoskeletal processes and decreases blood pressure.
Article
Virology
Zamaneh Hajikhezri, Yanina Kaira, Erik Schubert, Mahmoud Darweesh, Catharina Svensson, Goeran Akusjaervi, Tanel Punga
Summary: This study reveals that the cellular RNA-binding protein FXR1 regulates the stability of virus capsid mRNAs from the major late transcription unit (MLTU) in human adenovirus-5 (HAdV-5) infection. Depletion of FXR1 leads to increased steady-state levels of MLTU mRNAs. Surprisingly, the lack of FXR1 reduces viral capsid protein accumulation and formation of infectious virus progeny, indicating an opposing function of FXR1 in HAdV-5 infection.
JOURNAL OF VIROLOGY
(2023)
Article
Behavioral Sciences
Lauren M. Schmitt, Anna L. Arzuaga, Ashley Dapore, Jason Duncan, Maya Patel, John R. Larson, Craig A. Erickson, John A. Sweeney, Michael E. Ragozzino
Summary: This study found that individuals with fragile X syndrome (FXS) and Fmr1 knockout (KO) mice show similar learning impairments in cognitive flexibility. Male individuals with FXS exhibit deficits in both learning and reversal learning, while female individuals with FXS only show deficits in reversal learning. These findings have implications for advancing treatment development for FXS.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Review
Medicine, General & Internal
David O. Acero-Garces, Wilmar Saldarriaga, Ana M. Cabal-Herrera, Christian A. Rojas, Randi J. Hagerman
Summary: Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, leading to epigenetic changes and the silencing of gene expression. The absence of the protein FMRP, coded by this gene, results in cellular dysfunction and affects brain development and function. The disease can be diagnosed based on early physical and neurological manifestations, but molecular tests are required for confirmation. Fragile X syndrome has a significant impact on daily living and poses a burden for affected individuals and their families. It is the most common genetic cause of intellectual disability and autism spectrum disorder, and should be suspected in patients with neurodevelopmental delay. Early interventions can greatly improve the functional prognosis and quality of life for individuals with Fragile X syndrome, emphasizing the need for a multidisciplinary approach to healthcare.
Article
Psychiatry
Lauren Bullard, Danielle Harvey, Leonard Abbeduto
Summary: Previous research shows that characteristics of both the child and the mother impact maternal well-being and parenting stress in mothers of children with FXS. More work is needed with self-report measures supplemented by physiological measures. The study found elevated rates of depressive symptoms in mothers, with child externalizing behaviors being the primary correlate of maternal well-being.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
Randall M. Golovin, Jacob Vest, Kendal Broadie
Summary: The study reveals that FMRP controls the synaptic remodeling of olfactory sensory neurons in neuron-specific circuits during critical periods. Additionally, neural circuits can compensate for global FMRP loss to reinstate normal critical period brain circuit remodeling.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Genetics & Heredity
Aadil Yousuf, Nadeem Ahmed, Abrar Qurashi
Summary: Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X syndrome (FXS) are distinct disorders caused by abnormal expansion of CGG repeats. FXTAS is a neurodegenerative disorder characterized by gene hyperexpression, while FXS is a neurodevelopmental disorder characterized by gene silencing. Non-canonical DNA and RNA structures formed from CGG repeat expansions can disrupt cellular processes and have different effects in these two disorders.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Valentina La Cognata, Giovanna Morello, Sebastiano Cavallaro
Summary: Molecular and clinical heterogeneity pose challenges in the development of early diagnosis and effective treatment approaches for neurodegenerative diseases. Omics technologies offer a comprehensive view of molecular pathways, aiding in the differentiation of patient subtypes and advancing personalized medicine in neurology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Valentina La Cognata, Maria Guarnaccia, Giovanna Morello, Martino Ruggieri, Agata Polizzi, Sebastiano Cavallaro
Summary: Lysosomal storage diseases (LSDs) are a heterogeneous group of monogenic metabolic disorders with challenging diagnosis due to their variable clinical manifestations and genetic heterogeneity. Recent advancements in rapid diagnostic methods have made it possible for certain LSDs to be included in national newborn screening programs. Evaluation of a targeted next-generation sequencing panel designed for LSDs shows that it is a fast, accurate, and cost-effective process that can improve diagnostic speed and reduce costs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Elisabetta Anna Tendi, Maria Guarnaccia, Giovanna Morello, Sebastiano Cavallaro
Summary: Hyperphenylalaninemia (HPA) is a common amino acid metabolism disorder caused by defects in enzymes involved in phenylalanine metabolism, leading to the accumulation of phenylalanine and its secondary metabolites. Early diagnosis and treatment can improve the prognosis of affected patients. High-throughput molecular technologies can aid in accurate diagnosis and treatment determination.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Neurosciences
Lisa Bauer, Brigitta M. Laksono, Femke M. S. de Vrij, Steven A. Kushner, Oliver Harschnitz, Debby van Riel
Summary: This article provides an overview of neurological complications associated with SARS-CoV-2 infection and discusses their pathogenesis. It outlines the distinctions between neuroinvasiveness, neurotropism, and neurovirulence, and explores the advantages and limitations of different experimental models in advancing the field.
TRENDS IN NEUROSCIENCES
(2022)
Review
Health Care Sciences & Services
Giulia Gentile, Giovanna Morello, Valentina La Cognata, Maria Guarnaccia, Francesca Luisa Conforti, Sebastiano Cavallaro
Summary: Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by selective neuron degeneration, with a lack of effective biomarkers and therapies. MicroRNAs (miRNAs) have shown promise in diagnostics and therapy of these NDs due to their abnormal expression and ability to target multiple molecules and pathways.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Health Care Sciences & Services
Paola Ruffo, Sebastiano Cavallaro, Francesca Luisa Conforti
Summary: The application of omics sciences in clinical trials for motor neuron diseases is revolutionizing their diagnosis and therapy, providing new opportunities for personalized medicine.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Valentina La Cognata, Sebastiano Cavallaro
Summary: Lysosomal storage diseases (LSDs) are rare metabolic disorders characterized by the accumulation of non-degraded substances. Next-generation sequencing (NGS) provides a powerful tool for genetic testing in LSDs patients, allowing the detection of small and large genetic variations. However, the clinical application of NGS in diagnosing LSDs still faces challenges.
Article
Biology
Maria Guarnaccia, Laura Guarnaccia, Valentina La Cognata, Stefania Elena Navone, Rolando Campanella, Antonella Ampollini, Marco Locatelli, Monica Miozzo, Giovanni Marfia, Sebastiano Cavallaro
Summary: The study developed a targeted next-generation sequencing approach for analyzing genetic variations and chromosomal aberrations in gliomas, which can provide accurate and specific assessment of tumor pathogenesis, prognosis, and treatment response. This has important implications for the diagnosis and treatment of gliomas.
Article
Neurosciences
Lisa Bauer, Melanie Rissmann, Feline F. W. Benavides, Lonneke Leijten, Peter van Run, Lineke Begeman, Edwin J. B. Veldhuis Kroeze, Bas Lendemeijer, Hilde Smeenk, Femke M. S. de Vrij, Steven A. Kushner, Marion P. G. Koopmans, Barry Rockx, Debby van Riel
Summary: The Delta and Omicron BA.1 variants of SARS-CoV-2 exhibit reduced neuroinvasiveness and neurovirulence compared to the ancestral strain D614G, as shown in in vitro and in vivo experiments.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell Biology
Joost Schimmel, Nuria Munoz-Subirana, Hanneke Kool, Robin van Schendel, Sven van der Vlies, Juliette A. Kamp, Femke de Vrij, Steven A. Kushner, Graeme C. M. Smith, Simon J. Boulton, Marcel Tijsterman
Summary: Gene editing can be improved by inhibiting non-homologous end joining (NHEJ) or polymerase theta-mediated end joining (TMEJ), which alters the outcomes of CRISPR-Cas9. Inhibiting TMEJ activity using ART558 suppresses microhomology-driven deletions and promotes NHEJ-specific outcomes. Combining TMEJ and NHEJ inhibition increases the efficiency of precise gene editing through homology-driven repair (HDR).
Article
Biochemistry & Molecular Biology
Valentina Latina, Anna Atlante, Francesca Malerba, Federico La Regina, Bijorn Omar Balzamino, Alessandra Micera, Annabella Pignataro, Egidio Stigliano, Sebastiano Cavallaro, Pietro Calissano, Giuseppina Amadoro
Summary: In addition to deficits in hippocampal-dependent episodic memory, Alzheimer's Disease (AD) is characterized by sensory impairment in visual cognition due to extensive neuropathology in the retina. A monoclonal antibody called 12A12 has been found to specifically neutralize the harmful tau fragments associated with AD without affecting the normal protein. When administered to a mouse model of AD, 12A12 successfully reduces the accumulation of these tau fragments in the brain and retina, improving the associated symptoms. This study also reveals that 12A12 downregulates the expression of proteins involved in the production of amyloid beta, leading to a decrease in its accumulation in both the hippocampus and retina.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Giovanna Morello, Valentina La Cognata, Maria Guarnaccia, Velia D'Agata, Sebastiano Cavallaro
Summary: Transcriptional regulation is crucial in biological processes and can be deciphered through reverse-engineering programs. In this review, genomics is discussed as a tool to understand the complex and coordinated transcriptional programs controlling neuronal apoptosis and survival. Decrypting the neuronal fate code may provide insights for therapeutic approaches targeting downstream targets and regulatory networks in neurodegeneration and cancer.
Article
Cell Biology
Valentina La Cognata, Agata Grazia D'Amico, Grazia Maugeri, Giovanna Morello, Maria Guarnaccia, Benedetta Magri, Eleonora Aronica, Velia D'Agata, Sebastiano Cavallaro
Summary: Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron (MN) depletion. CXCR2 has been implicated in ALS pathology and its expression is increased in cortical neurons of sporadic ALS patients. Inhibition of CXCR2 prevents MN degeneration in vitro and improves neuromuscular function in SOD1-G93A mice.
Article
Cell Biology
Giovanna Morello, Valentina La Cognata, Maria Guarnaccia, Vincenzo La Bella, Francesca Luisa Conforti, Sebastiano Cavallaro
Summary: This study characterized transcriptome changes in skin fibroblasts of ALS patients and identified 277 differentially expressed transcripts that could serve as molecular biomarkers for ALS diagnosis.
Article
Biochemistry & Molecular Biology
Elisabetta Anna Tendi, Giovanna Morello, Maria Guarnaccia, Valentina La Cognata, Salvatore Petralia, Maria Anna Messina, Concetta Meli, Agata Fiumara, Martino Ruggieri, Sebastiano Cavallaro
Summary: Hyperphenylalaninemia (HPA) is a common genetic disorder characterized by serious clinical manifestations. Next-generation sequencing (NGS) technology can help identify the molecular basis of this disease due to its genetic and allelic heterogeneity. We developed a targeted NGS (tNGS) approach for detecting genetic variants associated with HPA, providing a comprehensive view and optimizing patient care.
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)
