Review
Biochemistry & Molecular Biology
Pavlina Hemerkova, Martin Valis
Summary: ALS is a neurodegenerative disease that affects motor neurons and currently has no cure. Free oxygen radicals are known to play a role in the pathogenesis of ALS, while antioxidant enzymes like SOD1 are crucial for antioxidant protection.
Article
Biochemistry & Molecular Biology
Venkatesan Santhanam, Priya Modi, Umesh K. Mishra, Ishrat Jahan, Namakkal G. Ramesh, Shashank Deep
Summary: In this study, the first iminosugar that inhibits superoxide dismutase fibrillation associated with ALS is reported. Novel triazole and tetrazole embedded iminosugars were successfully synthesized, and one of these designed iminosugars was found to inhibit SOD1 fibrillation and break pre-formed fibrils. Docking and MD simulation studies indicated that this compound interacts with the key residue Arg69 of SOD1 through hydrogen bonding.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Medicine, General & Internal
Teresa Cunha-Oliveira, Daniela Franco Silva, Luis Segura, Ines Baldeiras, Ricardo Marques, Tatiana Rosenstock, Paulo J. Oliveira, Filomena S. G. Silva
Summary: Distinct redox signatures were found in lymphoblasts from mutSOD1, undSOD1, and healthy controls, which can serve as therapeutic targets for ALS drug development. High heterogeneity in redox profiles between cohorts was observed, but clustering analysis successfully segregated healthy controls from ALS samples based on specific parameters. These findings provide valuable insights for understanding oxidative stress profiles in different forms of ALS and potential treatment strategies.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Clinical Neurology
Benjamin G. Trist, Sian Genoud, Stephane Roudeau, Alexander Rookyard, Amr Abdeen, Veronica Cottam, Dominic J. Hare, Melanie White, Jens Altvater, Jennifer A. Fifita, Alison Hogan, Natalie Grima, Ian P. Blair, Kai Kysenius, Peter J. Crouch, Asuncion Carmona, Yann Rufin, Stephane Claverol, Stijn Van Malderen, Gerald Falkenberg, David J. Paterson, Bradley Smith, Claire Troakes, Caroline Vance, Christopher E. Shaw, Safa Al-Sarraj, Stuart Cordwell, Glenda Halliday, Richard Ortega, Kay L. Double
Summary: This study examined the changes in SOD1 protein in post-mortem spinal cord tissues of ALS patients. The results showed mislocalization and accumulation of SOD1 protein in motor neurons of ALS patients, which was associated with instability and mismetallation of enzymatically active SOD1 dimers, as well as alterations to SOD1 post-translational modifications and molecular chaperones governing SOD1 maturation. These changes mostly occurred in regions of neurodegeneration and differentiated ALS patients from controls effectively.
Article
Neurosciences
Teresa Cunha-Oliveira, Marcelo Carvalho, Vilma Sardao, Elisabete Ferreiro, Debora Mena, Francisco B. Pereira, Fernanda Borges, Paulo J. Oliveira, Filomena S. G. Silva
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with mitochondrial alterations in lymphoblasts that may have diagnostic and therapeutic implications.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Karin M. Forsberg, Karin S. Graffmo, Erica Stenvall, Naima Tabikh, Stefan L. Marklund, Thomas Brannstrom, Peter M. Andersen
Summary: The D90A mutation in the SOD1 gene is associated with atypical features in amyotrophic lateral sclerosis, including slowly evolving motor symptoms, recessive heredity, and potential involvement of sensory, autonomic, and urinary bladder functions. This study reveals that neuropathological changes in patients with homozygous D90A mutation extend beyond the motor system to include cognitive and sensory cortical areas, but do not affect non-nervous organs.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Delia Gagliardi, Paolo Ripellino, Megi Meneri, Roberto Del Bo, Sara Antognozzi, Giacomo Pietro Comi, Claudio Gobbi, Antonia Ratti, Nicola Ticozzi, Vincenzo Silani, Dario Ronchi, Stefania Corti
Summary: In this study, the authors provided a clinical and molecular description of a cohort of SOD1-ALS patients, revealing the heterogeneity in clinical and molecular characteristics of SOD1 mutations. The cohort exhibited variable expressivity, atypical presentations, and different modes of inheritance. With the availability of SOD1-directed antisense oligonucleotide for SOD1-ALS patients, prompt screening for SOD1 mutations in ALS patients is recommended.
FRONTIERS IN NEUROLOGY
(2023)
Review
Cell Biology
Ilaria Martinelli, Elisabetta Zucchi, Cecilia Simonini, Giulia Gianferrari, Giovanna Zamboni, Marcello Pinti, Jessica Mandrioli
Summary: Although mutations in the SOD1 gene account for only a minority of ALS cases, the discovery of this gene has greatly expanded our understanding of the diverse pathogenic basis of ALS. This review focuses on cognitive impairment in SOD1-ALS patients and highlights the potential frailty of frontal lobe function in patients with different SOD1-ALS mutations. Thoroughly reviewing the reported mutations could contribute to a comprehensive genotype-phenotype correlation database for SOD1-ALS.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Shlomit Ezer, Muhannad Daana, Julien H. Park, Shira Yanovsky-Dagan, Ulrika Nordstrom, Adily Basal, Simon Edvardson, Ann Saada, Markus Otto, Vardiella Meiner, Stefan L. Marklund, Peter Munch Andersen, Tamar Harel
Summary: Pathogenic variants in the SOD1 gene are associated with a severe motor-neurological syndrome in infants, characterized by global developmental delay and movement impairments. This study identified a homozygous loss-of-function variant in the SOD1 gene in an infant with severe neurological symptoms. Further analysis showed that this variant leads to instability and degeneration of the SOD1 protein. The study highlights the importance of specific valine residues in the SOD1 protein and suggests implications for future therapeutic research.
Article
Chemistry, Multidisciplinary
Katelyn M. Baumer, Christopher D. Cook, Collin T. Zahler, Alexandra A. Beard, Zhijuan Chen, Jordan C. Koone, Chad M. Dashnaw, Raul A. Villacob, Touradj Solouki, John L. Wood, David R. Borchelt, Bryan F. Shaw
Summary: Repulsive electrostatic forces between prion-like proteins hinder aggregation, but compounds selectively boosting the negative charge of misfolded SOD1 were synthesized. These compounds showed slower aggregation of acetylated amyloid-SOD1 compared to unacetylated forms, and exhibited reactivity with other types of proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Clinical Neurology
Philippe Corcia, Christian Lunetta, Philippe Couratier, Patrick Vourc'h, Marta Gromicho, Claude Desnuelle, Marie-Helene Soriani, Susana Pinto, Mamede de Carvalho
Summary: The study found that PLS and ALS cases occurred in nine families, generally among first-degree relatives. Patients with both diseases exhibited typical disease characteristics, and genetic studies revealed mutations in specific genes in some patients. These results strongly support a phenotypic continuum between PLS and ALS.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Chemistry, Medicinal
Bini Mathew, Pedro Ruiz, Shilpa Dutta, Jordan T. Entrekin, Sixue Zhang, Kaval D. Patel, Micah S. Simmons, Corinne E. Augelli-Szafran, Rita M. Cowell, Mark J. Suto
Summary: ALS is a rare neurodegenerative disease with unknown cause, characterized by the gradual degeneration of motor neurons. Mutations in SOD1 and SOD2 genes are associated with ALS. Research has shown that hybrid compounds of SRI-22819 and Ataluren may have improved therapeutic effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chika Takashima, Yasuhiro Kosuge, Masahisa Inoue, Shin-Ichi Ono, Eiichi Tokuda
Summary: The study reveals that misfolded SOD1 is present in the cerebrospinal fluid of ALS patients and spreads through the extracellular environment of the central nervous system. Unlike intracellular misfolded SOD1, a conformational feature of extracellular misfolded SOD1 linked to prion-like properties has been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Nutrition & Dietetics
Yoshiaki Furukawa
Summary: This article reviews the copper and zinc binding process of SOD1 in vivo and discusses the potential of a copper chaperone for developing ALS therapeutics.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2022)
Article
Neurosciences
Yuxing Xia, Zhijuan Chen, Guilian Xu, David R. Borchelt, Jacob Ayers, Benoit Giasson
Summary: ALS is a progressive neurological disease caused by motor neuron degeneration, with SOD1 mutations leading to toxic aggregates in the brain and spinal cord. Monoclonal antibodies generated from SOD1 knockout mice can selectively detect denatured or aggregated SOD1, providing a potential tool for clinical diagnosis and passive immunotherapy for SOD1 ALS.
NEUROSCIENCE LETTERS
(2021)
Review
Chemistry, Multidisciplinary
Yoshiaki Furukawa
Summary: This review discusses the importance of metal binding and disulfide formation in Cu/Zn-superoxide dismutase (SOD1) for stabilizing protein structure and enzymatic function, as well as the potential link between failure of these processes and neurodegenerative diseases caused by protein misfolding.
Article
Neurosciences
Mikako Hirose, Mito Asano, Saori Watanabe-Matsumoto, Koji Yamanaka, Yoichiro Abe, Masato Yasui, Eiichi Tokuda, Yoshiaki Furukawa, Hidemi Misawa
Summary: The study indicates that abnormal expression and mislocalization of AQP4 in SOD1(G93A) mice result in dysfunction of the glymphatic system, leading to delayed waste clearance and exacerbation of ALS disease progression.
NEUROSCIENCE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Shintaro Kimura, Hiroaki Kamishina, Yoko Hirata, Kyoji Furuta, Yoshiaki Furukawa, Osamu Yamato, Sadatoshi Maeda, Yuji O. Kamatari
Summary: In neurodegenerative disorders, the aggregation of amyloidogenic proteins plays a crucial role in disease progression. Several novel compounds have been found to effectively inhibit aggregate formation of mutant superoxide dismutase 1 (cSOD1 E40K) in dogs and prion protein (hPrP) in humans, suggesting their potential as therapeutic candidates for amyloidogenic neurodegenerative disorders.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Biochemistry & Molecular Biology
Michiko Tajiri, Hiroto Aoki, Atsuko Shintani, Kaori Sue, Satoko Akashi, Yoshiaki Furukawa
Summary: Cu/Zn-superoxide dismutase (SOD1) can bind a non-stoichiometric amount of copper and zinc ions, forming a homodimer with a stochastic combination of subunits. Correct metallation of SOD1 is important for amyotrophic lateral sclerosis.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biology
Yukio Imamura, Ayami Okuzumi, Saki Yoshinaga, Akiko Hiyama, Yoshiaki Furukawa, Tomohiro Miyasaka, Nobutaka Hattori, Nobuyuki Nukina
Summary: In this study, alpha-synuclein preformed fibrils (PFF) were labeled with quantum dots, allowing for the visualization of their movement in brain tissue slices. The trafficking of alpha-syn seeds was found to depend on fast axonal transport, while seed spreading was dependent on endocytosis and neuronal activity. Pharmacological effects on alpha-syn seed spreading were also observed, with drugs such as riluzole effectively reducing seed spread both in vitro and in vivo.
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Takehisa Hirayama, Mari Shibukawa, Masaru Yanagihashi, Hitoshi Warita, Naoki Atsuta, Koji Yamanaka, Osamu Kano
Summary: This study comprehensively investigated the non-motor symptoms of amyotrophic lateral sclerosis (ALS) and found that fatigue and pain were the most common symptoms. The study also indicated that many non-motor symptoms affect the quality of life of ALS patients.
ACTA NEUROLOGICA BELGICA
(2023)
Article
Biochemistry & Molecular Biology
Yoshiaki Furukawa, Kyoka Matsumoto, Kenta Nakagome, Atsuko Shintani, Kaori Sue
Summary: The copper chaperone CCS interacts specifically with another copper chaperone HAH1 through its N-terminal domain CCSdI. This interaction is not involved in the copper supply to SOD1 but is mediated by zinc ions coordinated with the CxxC motifs in CCSdI and HAH1. The study suggests that CCSdI may play a role in metal-mediated interactions with other proteins, including heterologous copper chaperones.
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kei Hashimoto, Seiji Watanabe, Masato Akutsu, Norifumi Muraki, Hiroaki Kamishina, Yoshiaki Furukawa, Koji Yamanaka
Summary: Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease in dogs that shares clinical and genetic features with amyotrophic lateral sclerosis, a human motor neuron disease. Mutations in the SOD1 gene cause both canine DM and a subset of inherited human amyotrophic lateral sclerosis. The E40K mutation is the most common DM-causing mutation in dogs, but its specific mechanism of inducing SOD1 aggregation is still unknown.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Noe Kawade, Koji Yamanaka
Summary: Alzheimer's disease is the most common cause of dementia, and genetic studies have shown a link between lipid metabolism genes and the disease. Epidemiological studies have also found altered lipid levels in the brains of Alzheimer's patients. These findings suggest that lipid metabolism changes in the brain may contribute to the exacerbation of Alzheimer's pathology.
Review
Immunology
Akira Sobue, Okiru Komine, Koji Yamanaka
Summary: Alzheimer's disease is a common form of dementia characterized by senile plaques and neurofibrillary tangles. Recent studies have found that immune response genes in microglia are associated with AD risk. This study compared gene expression profiles of microglia in different mouse models and human brains with early AD pathology, aiming to identify potential therapeutic targets for AD.
INFLAMMATION AND REGENERATION
(2023)
Article
Clinical Neurology
Takehisa Hirayama, Mari Shibukawa, Harumi Morioka, Masamichi Hozumi, Hiroshi Tsuda, Naoki Atsuta, Yuishin Izumi, Yuki Nakayama, Toshio Shimizu, Haruhisa Inoue, Makoto Urushitani, Koji Yamanaka, Masashi Aoki, Satoru Ebihara, Atsushi Takeda, Osamu Kano
Summary: This study investigated disaster preparation among patients with ALS and their caregivers in Japan. The results showed that most respondents were not adequately prepared for disasters, especially those without ventilators. Therefore, there is a need for better education regarding disaster preparedness for these groups.
JOURNAL OF CLINICAL NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Kotaro Oiwa, Seiji Watanabe, Kazunari Onodera, Yohei Iguchi, Yukako Kinoshita, Okiru Komine, Akira Sobue, Yohei Okada, Masahisa Katsuno, Koji Yamanaka
Summary: This study reveals that impaired dimerization/multimerization of TAR DNA binding protein-43 (TDP-43) is a key factor in the pathology of amyotrophic lateral sclerosis (ALS). N-terminal dimerization-deficient TDP-43 forms pathological inclusion bodies in ALS motor neurons. The expression of this mutant TDP-43 in cells recapitulates TDP-43 pathology, including cytoplasmic mislocalization and aggregate formation. Additionally, a bimolecular luminescence complementation reporter assay can detect reduced N-terminal dimerization of TDP-43 before pathological changes occur.
Article
Chemistry, Analytical
Hideto Moriyama, Genki Ogata, Haruma Nashimoto, Seishiro Sawamura, Yoshiaki Furukawa, Hiroshi Hibino, Hiroyuki Kusuhara, Yasuaki Einaga
Summary: Monitoring drug concentration in blood is crucial for safe and effective drug treatment. This study introduces a rapid electrochemical method using boron-doped diamond electrodes to determine the unbound drug concentration in human serum. The results show that this method can provide fast and reliable measurement within the clinical concentration range.
Review
Nutrition & Dietetics
Yoshiaki Furukawa
Summary: This article reviews the copper and zinc binding process of SOD1 in vivo and discusses the potential of a copper chaperone for developing ALS therapeutics.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2022)
