Article
Endocrinology & Metabolism
Sean-Patrick Riechers, Jelena Mojsilovic-Petrovic, Tayler B. Belton, Ram P. Chakrabarty, Mehraveh Garjani, Valentina Medvedeva, Casey Dalton, Yvette C. Wong, Navdeep S. Chandel, Gerald Dienel, Robert G. Kalb
Summary: The study investigates the metabolism of neurons expressing familial ALS genes and finds that in rodent models of fALS, there is a rewiring of metabolism with reduced neuronal lactate production and maintained or enhanced activity of the neuronal citric acid cycle. This suggests that targeting fuel utilization adjustments in neurodegenerative diseases associated with mitochondrial dysfunction can be beneficial.
MOLECULAR METABOLISM
(2022)
Review
Biochemistry & Molecular Biology
Caterina Peggion, Valeria Scalcon, Maria Lina Massimino, Kelly Nies, Raffaele Lopreiato, Maria Pia Rigobello, Alessandro Bertoli
Summary: ALS is a fatal neurodegenerative disorder characterized by the loss of motor neurons in the brain and spinal cord. Mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been found to be related to ALS, affecting non-neuronal cells, such as glial and skeletal muscle cells, and leading to alterations in redox balance and Ca2+ homeostasis. These effects contribute to the progression of ALS.
Article
Biochemistry & Molecular Biology
Mikayla L. Brown, Luke McAlary, Jeremy S. Lum, Natalie E. Farrawell, Justin J. Yerbury
Summary: CuATSM has shown therapeutic effectiveness in ALS mouse models, but only for wild-type-like SOD1 mutants. It has genotype-specific effects and can cause adverse events at high doses. The therapeutic window of CuATSM depends on the specific variant of the SOD1 mutant and the availability of copper-depleted SOD1.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Clinical Neurology
W. Camu, E. De La Cruz, F. Esselin
Summary: Familial ALS (FALS) accounts for 10 to 15% of ALS cases. Gene-specific therapy, such as antisense oligonucleotides (ASO) and viral vectors, has shown promising results in animal models, particularly in targeting SOD1 gene mutations. However, the use of viral vectors in humans is limited due to immunogenicity. Antibody-based therapies and modulation of microbiota have also shown potential in treating FALS. The landscape of experimental FALS treatment is rapidly evolving, and human clinical trials are ongoing.
REVUE NEUROLOGIQUE
(2023)
Article
Clinical Neurology
Jing Ma, Xiaomin Pang, Shan Huang, Jing Zhang, Juan Wang, Rongjuan Zhao, Xueli Chang, Junhong Guo, Wei Zhang
Summary: The study aimed to investigate genetic characteristics in Chinese patients with familial or young-onset ALS, identifying two novel mutations. Patients with familial or young-onset ALS often carried related gene mutations, suggesting routine genetic sequencing should be performed.
NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Munishikha Kalia, Mattia Miotto, Deborah Ness, Sarah Opie-Martin, Thomas P. Spargo, Lorenzo Di Rienzo, Tommaso Biagini, Francesco Petrizzelli, Ahmad Al Khleifat, Renata Kabiljo, Tommaso Mazza, Giancarlo Ruocco, Edoardo Milanetti, Richard J. B. Dobson, Ammar Al-Chalabi, Alfredo Iacoangeli
Summary: This study investigates the influence of SOD1 gene mutations on the clinical phenotype of ALS. By analyzing structural and dynamic differences as well as clinical data, it was found that patients carrying MBR variants generally have a longer survival time compared to those with WTL variants. The results support the hypothesis of a decoupling between mechanisms of onset and progression of SOD1 ALS.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Genetics & Heredity
Xinmei Wen, Wenjia Zhu, Nan L. Xia, Qianwen Li, Li Di, Shu Zhang, Hai Chen, Yan Lu, Min Wang, Min Xu, Suobin Wang, Xin-Ming Shen, Jie Lu, Yuwei Da
Summary: Amyotrophic lateral sclerosis (ALS) is a common motor neuron disease with diverse clinical presentations and genetic causes. Different missense mutations in the SOD1 gene have been identified to cause familial ALS, and a novel mutation may lead to fast-deteriorating pure lower motor neuron symptoms. Modeling of all R116 substitutions in the SOD1 protein structure showed a shared mechanism of destroyed hydrogen bonds, potentially resulting in neurotoxicity.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Sandrine Lenglez, Ariane Sablon, Gilles Fenelon, Anne Boland, Jean-Francois Deleuze, Claire Boutoleau-Bretonniere, Gael Nicolas, Jean-Baptiste Demoulin
Summary: This study conducted a comprehensive molecular analysis and functional studies on PDGFRB gene variants associated with primary familial brain calcification, identifying pathogenic variants and discussing the relationship between residual activity of variants, incomplete penetrance, brain calcification, and neurological symptoms.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Jennifer L. Shadrach, Wesley M. Stansberry, Allison M. Milen, Rachel E. Ives, Elizabeth A. Fogarty, Anthony Antonellis, Brian A. Pierchala
Summary: After peripheral nerve injuries, motor neurons mount robust regenerative responses, while they selectively degenerate in diseases like ALS. Studies have shown that the upregulation of certain genes in nerve injury and ALS models is context specific, with chemokines potentially playing an important role in motor neurons.
Article
Biochemistry & Molecular Biology
Marcella Nunziato, Anna Balato, Anna Ruocco, Valeria D'Argenio, Roberta Di Caprio, Nicola Balato, Fabio Ayala, Francesco Salvatore
Summary: Psoriasis is a chronic skin disorder with an immune basis, characterized by red, flaky patches that often release silvery scales. The study aimed to determine if there are genetic alterations that can explain the onset of the disease by using next-generation sequencing technologies and a multigene panel. Variants associated with psoriasis were found in the TRAF3IP2 gene, and a missense variant was found in the NAT9 gene. The use of multigene panels can help identify new susceptibility genes and allow for early diagnoses in affected families.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Eanna B. Ryan, Jianhua Yan, Nimrod Miller, Sudarshan Dayanidhi, Yongchao C. Ma, Han-Xiang Deng, Teepu Siddique
Summary: Mutations in the CHCHD10 gene have been linked to various degenerative diseases, including ALS. Transgenic mice overexpressing an ALS-linked CHCHD10 mutation showed an abbreviated lifespan and exhibited pathology in the CNS, skeletal muscle, and cardiac tissue. The study provides insights into the pathogenesis of CHCHD10-related disorders, suggesting a contribution of CNS, skeletal muscle, and cardiac pathology to the disease.
Article
Genetics & Heredity
Angela Sparago, Flavia Cerrato, Laura Pignata, Francisco Cammarata-Scalisi, Livia Garavelli, Carmelo Piscopo, Alessandra Vancini, Andrea Riccio
Summary: Beckwith-Wiedemann syndrome (BWS) is characterized by overgrowth, organomegaly, abdominal wall defects, and tumor predisposition, with CDKN1C gene playing a crucial role. Novel CDKN1C variants are associated with different clinical manifestations, with frameshift and nonsense variants leading to more severe phenotypes.
Article
Geriatrics & Gerontology
Yingzi Liu, Xuewen Xiao, Hui Liu, Xinxin Liao, Yafang Zhou, Ling Weng, Lu Zhou, Xixi Liu, Xiang-yun Bi, Tianyan Xu, Yuan Zhu, Qijie Yang, Sizhe Zhang, Xiaoli Hao, Weiwei Zhang, Junling Wang, Bin Jiao, Lu Shen
Summary: Alzheimer's disease is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Mutations in the amyloid protein precursor gene (APP) are known to be pathogenic for familial Alzheimer's disease. Although patients with APP mutations show more non-demented symptoms and neurological symptoms, their clinical phenotypes are generally consistent with typical AD. Genotype-phenotype analysis based on APP processing differences caused by mutations revealed differences in onset age, behavioral and psychological disorders of dementia, and myoclonus.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biophysics
Brianna Hnath, Nikolay Dokholyan
Summary: Toxic SOD1 trimers, competing with protective fibril formation, have been identified as off-pathway intermediates. Stabilizing the trimeric SOD1 can prevent fibril formation, making it a potential therapeutic approach for ALS.
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Mark Bustoros, Shankara Anand, Romanos Sklavenitis-Pistofidis, Robert Redd, Eileen M. Boyle, Benny Zhitomirsky, Andrew J. Dunford, Yu-Tzu Tai, Selina J. Chavda, Cody Boehner, Carl Jannes Neuse, Mahshid Rahmat, Ankit Dutta, Tineke Casneuf, Raluca Verona, Efstathis Kastritis, Lorenzo Trippa, Chip Stewart, Brian A. Walker, Faith E. Davies, Meletios-Athanasios Dimopoulos, P. Leif Bergsagel, Kwee Yong, Gareth J. Morgan, Francois Aguet, Gad Getz, Irene M. Ghobrial
Summary: This study identifies six distinct molecular and clinical subtypes of smoldering multiple myeloma (SMM) using genetic alterations analysis. Three of these subtypes are associated with an increased risk of progression to active multiple myeloma.
NATURE COMMUNICATIONS
(2022)
Review
Biotechnology & Applied Microbiology
Paul N. Valdmanis, Mark A. Kay
HUMAN GENE THERAPY
(2017)
Article
Multidisciplinary Sciences
Paul N. Valdmanis, Hak Kyun Kim, Kirk Chu, Feijie Zhang, Jianpeng Xu, Elizabeth M. Munding, Jia Shen, Mark A. Kay
NATURE COMMUNICATIONS
(2018)
Article
Clinical Neurology
Jacquelyn E. Braggin, Stephanie A. Bucks, Meredith M. Course, Carole L. Smith, Bryce Sopher, Leah Osnis, Kiel D. Shuey, Kimiko Domoto-Reilly, Christina Caso, Chizuru Kinoshita, Kathryn P. Scherpelz, Chloe Cross, Thomas Grabowski, Seyyed H. M. Nik, Morgan Newman, Gwenn A. Garden, James B. Leverenz, Debby Tsuang, Caitlin Latimer, Luis F. Gonzalez-Cuyar, Christopher Dirk Keene, Richard S. Morrison, Kristoffer Rhoads, Ellen M. Wijsman, Michael O. Dorschner, Michael Lardelli, Jessica E. Young, Paul N. Valdmanis, Thomas D. Bird, Suman Jayadev
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2019)
Article
Multidisciplinary Sciences
Meredith M. Course, Kathryn Gudsnuk, Paul N. Valdmanis
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Oncology
Chang Li, Meredith M. Course, Iain A. McNeish, Charles W. Drescher, Paul N. Valdmanis, Andre Lieber
Article
Biotechnology & Applied Microbiology
Gustavo de Alencastro, Katja Pekrun, Paul Valdmanis, Matthew Tiffany, Jianpeng Xu, Mark A. Kay
HUMAN GENE THERAPY
(2020)
Article
Cell Biology
Hak Kyun Kim, Jianpeng Xu, Kirk Chu, Hyesuk Park, Hagoon Jang, Pan Li, Paul N. Valdmanis, Qiangfeng Cliff Zhang, Mark A. Kay
Article
Medicine, Research & Experimental
Meredith M. Course, Kathryn Gudsnuk, Nitin Desai, Joel R. Chamberlain, Paul N. Valdmanis
MOLECULAR THERAPY-NUCLEIC ACIDS
(2020)
Article
Genetics & Heredity
Meredith M. Course, Kathryn Gudsnuk, Samuel N. Smukowski, Kosuke Winston, Nitin Desai, Jay P. Ross, Arvis Sulovari, Cynthia Bourassa, Dan Spiegelman, Julien Couthouis, Chang-En Yu, Debby W. Tsuang, Suman Jayadev, Mark A. Kay, Aaron D. Gitler, Nicolas Dupre, Evan E. Eichler, Patrick A. Dion, Guy A. Rouleau, Paul N. Valdmanis
AMERICAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Neurosciences
Giulia Monti, Mads Kjolby, Anne Mette G. Jensen, Mariet Allen, Juliane Reiche, Peter L. Moller, Raquel Comaposada-Baro, Bartlomiej E. Zolkowski, Carmen Vieira, Margarita Melnikova Jorgensen, Ida E. Holm, Paul N. Valdmanis, Niels Wellner, Christian B. Vaegter, Sarah J. Lincoln, Anders Nykjaer, Nilufer Ertekin-Taner, Jessica E. Young, Mette Nyegaard, Olav M. Andersen
Summary: This study identified a novel exon in SORL1 transcript encoding a truncated protein, which showed significantly reduced levels in the cerebellum of AD patients. These findings suggest potential synaptic functions for SORL1-38b in the brain.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Meredith M. Course, Arvis Sulovari, Kathryn Gudsnuk, Evan E. Eichler, Paul N. Valdmanis
Summary: The study identified 467 human-specific expansion VNTRs that are structurally organized with repeated motifs and affected by frequent deletion and duplication events. While most VNTRs maintain stable length across superpopulations, there are exceptions with significant differences in repeat composition and length between certain VNTRs. The findings suggest that repeat motif variability, composition, and length are crucial factors to consider when characterizing VNTRs and their impact on genomic variation.
Article
Cell Biology
Alec S. T. Smith, Changho Chun, Jennifer Hesson, Julie Mathieu, Paul N. Valdmanis, David L. Mack, Byung-Ok Choi, Deok-Ho Kim, Mark Bothwell
Summary: Gene editing technologies can enhance modeling of inheritable neurodegenerative diseases, but careful comparison of multiple cell lines is needed to ensure consistency and accuracy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Samuel N. Smukowski, Heather Maioli, Caitlin S. Latimer, Thomas D. Bird, Suman Jayadev, Paul N. Valdmanis
Summary: Amyotrophic lateral sclerosis (ALS) is a prominent motor neuron disease in humans. Several causative genes have been identified, and additional variants are being studied for their association with ALS. Understanding ALS genetics can lead to the development of effective treatments.
NEUROLOGY-GENETICS
(2022)
Article
Clinical Neurology
Meredith M. Course, Kathryn Gudsnuk, C. Dirk Keene, Thomas D. Bird, Suman Jayadev, Paul N. Valdmanis
Summary: Course et al. performed targeted long-read isoform-sequencing of PSEN1 and PSEN2 in individuals with sporadic Alzheimer's disease, familial Alzheimer's disease with PSEN1 and PSEN2 pathogenic variants, and controls. The study revealed unique aberrant splicing of PSEN2 in sporadic Alzheimer's disease, expanding our understanding of PSEN1 and PSEN2 variants in Alzheimer's disease and suggesting novel mechanisms of Alzheimer's disease pathogenesis.
Review
Biochemistry & Molecular Biology
Saebyeol Lee, Jungeun Kim, Paul N. N. Valdmanis, Hak Kyun Kim
Summary: Transfer RNAs (tRNAs) play a crucial role in mRNA translation by delivering amino acids to polypeptide chains. tRNAs can be cleaved by ribonucleases, resulting in tRNA-derived small RNAs (tsRNAs) with various regulatory functions. tsRNAs have been shown to have both oncogenic and tumor suppressor functions, and their abnormal expression and modifications are associated with various diseases. In this review, the biogenesis, gene regulation mechanisms, and potential therapeutic roles of tsRNAs in cancer are discussed.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)