Article
Biology
Achinta Sannigrahi, Sourav Chowdhury, Bidisha Das, Amrita Banerjee, Animesh Halder, Amaresh Kumar, Mohammed Saleem, Athi N. Naganathan, Sanat Karmakar, Krishnananda Chattopadhyay
Summary: Research shows that the stability and aggregation behavior of SOD1 in membrane environment are affected by Zn, not Cu. Two loop regions play a role in membrane attachment of SOD1 and aggregation driven by lipid-induced conformational changes.
Article
Multidisciplinary Sciences
Liangzhong Lim, Jian Kang, Jianxing Song
Summary: This study reveals the role of cations in the initial folding of hSOD1. Most cations, including Zn2+ mimics, showed negligible binding or induction for folding of nascent hSOD1. Cu2+ exhibited extensive binding to the unfolded state but led to severe aggregation. Surprisingly, Fe2+ was found to have Zn2+-like folding-inducing capacity.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Tania M. Manieri, Stefano L. Sensi, Rosanna Squitti, Giselle Cerchiaro
Summary: The study altered the activity of SOD1 in AD patients by modifying its zinc complexation capacity, leading to decreased enzymatic activity even when complexed with copper. The mutant SOD1 presented instability in zinc and copper coordination, making it a valuable in vitro model for studying SOD1 behavior in AD patients.
Article
Multidisciplinary Sciences
Xiaowen Wang, Hong Zhang, Russell Sapio, Jun Yang, Justin Wong, Xin Zhang, Jessie Y. Guo, Sharon Pine, Holly Van Remmen, Hong Li, Eileen White, Chen Liu, Megerditch Kiledjian, Dimitri G. Pestov, X. F. Steven Zheng
Summary: The study reveals a crucial role of nuclear SOD1 in ribosome biogenesis and proliferation in KRAS-driven lung cancer.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Ping Lu, Hua-Juan Yan, Cui Yang, Wen-Cai Feng, Fei Hu, Yue-Ying Wu, Wei-Wen Sun, Mei-Mei Gao, Yue-Sheng Long
Summary: The research suggests that high fat consumption leads to the generation of reactive oxygen species, decreases copper/zinc superoxide dismutase activity, and promotes neurodegeneration. Additionally, it was shown that saturated fatty acid palmitic acid decreases copper chaperone CCS levels, potentially leading to a decrease in SOD1 activity.
Article
Multidisciplinary Sciences
Li-Qiang Wang, Yeyang Ma, Han-Ye Yuan, Kun Zhao, Mu-Ya Zhang, Qiang Wang, Xi Huang, Wen-Chang Xu, Bin Dai, Jie Chen, Dan Li, Delin Zhang, Zhengzhi Wang, Liangyu Zou, Ping Yin, Cong Liu, Yi Liang
Summary: The authors determined the cryo-EM structure of SOD1 fibrils, providing insights into the conversion of SOD1 during the pathogenesis of ALS.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Danica Tasic, Milos Opacic, Sanja Kovacevic, Aleksandra Nikolic Kokic, Milena Dimitrijevic, Dusan Nikolic, Danijela Vojnovic Milutinovic, Dusko Blagojevic, Ana Djordjevic, Jelena Brkljacic
Summary: The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. This study found that fructose, independent of stress, decreased renal copper level and modulated renal copper metabolism to preserve vital cellular function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Biochemistry & Molecular Biology
Haihua Wu, Jing Liu, Xuhan Zhang, Xueyao Zhang, Jianzhen Zhang, Enbo Ma
Summary: In this study, four alternative splicing transcripts of icCuZnSOD1 in Oxya chinensis were identified, showing differences in heat resistance and antioxidant capacity. These variants exhibited varied expression patterns during developmental stages and in different tissues, with distinct responses to CuCl2 and ZnSO4. The transcripts played roles in defense against CdCl2-induced oxidative stress, with OcicCuZnSOD1a exhibiting the strongest antioxidant capacity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Plant Sciences
Handa Song, Borong Lin, Qiuling Huang, Longhua Sun, Jiansong Chen, Lili Hu, Kan Zhuo, Jinling Liao
Summary: A novel plant pathogen effector MgMO289 was found to increase susceptibility to Meloidogyne graminicola by utilizing the host O-2(center dot-)-scavenging system to suppress plant immunity.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
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)
Article
Multidisciplinary Sciences
Hong Yien Tan, Yean Kong Yong, Yuan Chao Xue, Huitao Liu, Tomomi Furihata, Esaki Muthu Shankar, Chen Seng Ng
Summary: Neuroinflammation worsens the development of ALS caused by SOD1 mutation. The mitochondrial damage triggered by ALS leads to the release of mtDNA and RNA:DNA hybrids, activating the IRF3- and IFNAR-dependent IFN-I and interferon-stimulating genes, causing high levels of IFN-I and pro-inflammatory response. Inter-neuronal gap junctions amplify the response through cGAS/DDX41-STING signaling. This highlights the role of a common DNA sensing pathway between SOD1 and TDP-43 in ALS progression.
Article
Biochemical Research Methods
Bing Zhao, Xinyu Bian, Xiaoyu Zhuang, Shu Liu, Zhiqiang Liu, Fengrui Song
Summary: This study revealed that the binding of liquiritin apioside can stabilize apo-SOD1 dimer and inhibit the aggregation of apo-SOD1. Native ESI-IM-MS is a powerful tool for investigating the structure-activity relationship between small molecules and proteins, and screening protein conformation stabilizers.
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2022)
Article
Chemistry, Multidisciplinary
Sunil Kumar Vimal, Hongyi Cao, Amit Dubey, Lokesh Agrawal, Nishit Pathak, Hua Zuo, Deepak Kumar, Sanjib Bhattacharyya
Summary: This study evaluated the pharmacological potential of a synthesized Au-PEG nanoconjugate in a transgenic mouse model of ALS. The results showed that Au-PEG treatment extended survival, delayed disease onset, and improved motor performance. Furthermore, molecular docking studies revealed that the addition of gold nanoparticles enhanced the binding affinity of kinesin to tubulin, restoring motor function.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Physical
Josieli Demetrio Siqueira, Sidnei Flores de Pellegrin, Letcia Paiva Fioravanco, Liniquer Andre Fontana, Bernardo Almeida Iglesias, Otavio Augusto Chaves, Davi Fernando Back
Summary: This study describes the synthesis, crystal structure, antioxidant activity, and molecular modeling calculations for two Cu-II complexes obtained from the condensation of ortho-vanillin with furfurylamine. Both complexes catalyzed superoxide dismutation and were evaluated and quantified by nitro blue tetrazolium photoreduction. Despite the unusual arrangement of the heptamer, it did not show the expected multiplicative activity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Diane Moujalled, Adam G. Southon, Eiman Saleh, Kerstin Brinkmann, Francine Ke, Melinda Iliopoulos, Ryan S. Cross, Misty R. Jenkins, Duong Nhu, Zilu Wang, Melissa X. Shi, Ruth M. Kluck, Guillaume Lessene, Stephanie Grabow, Ashley Bush, Andreas Strasser
Summary: BH3 mimetic drugs have the potential to trigger programmed cell death (PCD) and improve the treatment of glioblastoma multiforme (GBM). Co-targeting the pro-survival proteins BCL-XL and MCL-1 is more effective in killing GBM cells compared to conventional therapy, and combining with inducers of ferroptosis enhances the cell killing effect.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Mark A. Greenough, Darius J. R. Lane, Rachelle Balez, Helena Targa Dias Anastacio, Zhiwen Zeng, Katherine Ganio, Christopher A. McDevitt, Karla Acevedo, Abdel Ali Belaidi, Jari Koistinaho, Lezanne Ooi, Scott Ayton, Ashley Bush
Summary: Presenilin mutations may promote neurodegeneration through derepressing ferroptosis and have implications for the treatment of Alzheimer's disease.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Jae Pyun, Lachlan E. McInnes, Paul S. Donnelly, Celeste Mawal, Ashley Bush, Jennifer L. Short, Joseph A. Nicolazzo
Summary: The study found that copper II (ATSM) and copper II (GTSM) were able to modulate the expression and function of P-gp at the blood-brain barrier. Copper II (ATSM) significantly enhanced the expression and function of P-gp, while copper II (GTSM) reduced the expression and function of P-gp. This has important implications for brain drug delivery and clearance of Aβ.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Abdel Ali Belaidi, Shashank Masaldan, Adam Southon, Pawel Kalinowski, Karla Acevedo, Ambili T. Appukuttan, Stuart Portbury, Peng Lei, Puja Agarwal, Sue E. Leurgans, Julie Schneider, Marcus Conrad, Ashley Bush, Scott Ayton
Summary: Allelic variation to the APOE gene is the greatest genetic risk for sporadic Alzheimer's disease. Recent studies have found a link between APOE gene and brain iron, potentially through the ferroptosis pathway, to explain disease progression. Researchers discovered that apoE acts as a potent inhibitor of ferroptosis through activation of the PI3K/AKT pathway. Another study revealed that the APOE-epsilon 4 allele is more strongly associated with iron-related Alzheimer's disease, possibly due to lower levels of apoE protein and higher levels of polyunsaturated fatty acids.
MOLECULAR PSYCHIATRY
(2022)
Review
Geriatrics & Gerontology
Francesca M. Alves, Scott Ayton, Ashley Bush, Gordon S. Lynch, Rene Koopman
Summary: Sarcopenia is an age-related condition characterized by the progressive loss of muscle mass and strength, leading to frailty, increased risk of hospitalization and mortality, and increased healthcare costs. The review outlines the mechanisms of iron accumulation in muscle and evaluates the evidence for the role of iron overload in sarcopenia.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Clinical Neurology
Scott Ayton, Shorena Janelidze, Pawel Kalinowski, Sebastian Palmqvist, Abdel Ali Belaidi, Erik Stomrud, Anne Roberts, Blaine Roberts, Oskar Hansson, Ashley Ian Bush
Summary: This study investigates the association between iron, inflammation, apolipoprotein, and Alzheimer's disease. It suggests that iron is closely associated with apolipoprotein E and tau pathology, and plays different roles in different stages of the disease, correlating with cognitive deterioration.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Neurosciences
Sara Nikseresht, James B. W. Hilton, Jeffrey R. Liddell, Kai Kysenius, Ashley I. Bush, Scott Ayton, HuiJing Koay, Paul S. Donnelly, Peter J. Crouch
Summary: The permeable copper(II) compound is being investigated as a potential treatment for neurodegenerative diseases. The compound accumulates in affected areas of the central nervous system in patients, and studies have shown positive outcomes with transdermal application. This study compared the tissue copper concentrations in mice after oral and transdermal administration, revealing higher concentrations with transdermal application of soluble CuII(atsm). The results suggest that transdermal application could be a viable alternative to oral administration.
Review
Biochemistry & Molecular Biology
Darius J. R. Lane, Francesca Alves, Scott J. J. Ayton, Ashley I. I. Bush
Summary: The lack of disease-modifying treatments for Alzheimer's disease (AD) highlights the need for new biological models of disease progression and neurodegeneration. Oxidation of macromolecules within the brain, as well as dysregulation of redox-active metals like iron, are believed to contribute to AD pathophysiology. Creating a unified model of disease progression based on iron and redox dysregulation could lead to new therapeutic targets with disease-modifying potential.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Editorial Material
Neurosciences
Boyd Kenkhuis, Ashley I. Bush, Scott Ayton
Summary: Iron overload has been recognized as a factor in neurodegenerative diseases, with microglia being particularly susceptible to iron overload-induced ferroptosis, as revealed by recent research. The evidence of microglial ferroptosis in clinical specimens suggests that inhibitors of ferroptosis may have therapeutic potential for these diseases.
TRENDS IN NEUROSCIENCES
(2023)
Article
Medicine, Research & Experimental
Md Jakaria, Abdel A. Belaidi, Ashley I. Bush, Scott Ayton
Summary: Vitamin A and its metabolites can inhibit cell death caused by iron-dependent phospholipid peroxidation. They directly trap lipid radicals in ferroptosis, showing neuroprotective effects.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Jae Pyun, Huijing Koay, Pranav Runwal, Celeste Mawal, Ashley I. Bush, Yijun Pan, Paul S. Donnelly, Jennifer L. Short, Joseph A. Nicolazzo
Summary: Cu(ATSM) enhances the expression and function of P-gp at the blood-brain barrier, which has important implications for CNS drug delivery and clearance of A beta in AD.
Article
Telecommunications
Denzil Furtado, Andre F. Gygax, Chien Aun Chan, Ashley I. Bush
Summary: Situated at the intersection of technology and medicine, the Internet of Things (IoT) holds the promise of addressing some of healthcare's most pressing challenges. However, the successful implementation of IoT healthcare initiatives has been slow. To promote collaboration, a problem-oriented approach to developing healthcare technologies is proposed. Fog computing is suggested as the most promising technological paradigm for building a robust and scalable healthcare IoT ecosystem.
DIGITAL COMMUNICATIONS AND NETWORKS
(2023)
Article
Materials Science, Biomaterials
Joshua P. Morrow, David Pizzi, Zihnil A. I. Mazrad, Ashley I. Bush, Kristian Kempe
Summary: In this study, drug/cargo-free anti-ferroptotic nanomaterials were discovered, which can perturb the cell death process of ferroptosis by reducing lipid-peroxidation, highlighting their potential for therapy of ferroptosis-associated diseases and the role of nanocarriers in a therapeutic context.
BIOMATERIALS SCIENCE
(2023)
Article
Clinical Neurology
Vincent Dore, James D. Doecke, Ziad S. Saad, Gallen Triana-Baltzer, Randy Slemmon, Natasha Krishnadas, Pierrick Bourgeat, Kun Huang, Samantha Burnham, Christopher Fowler, Stephanie R. Rainey-Smith, Ashley I. Bush, Larry Ward, Jo Robertson, Ralph N. Martins, Colin L. Masters, Victor L. Villemagne, Jurgen Fripp, Hartmuth C. Kolb, Christopher C. Rowe
Summary: This study evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) and found that plasma P-217+tau levels elevate early in the AD continuum and correlate well with A beta and tau PET.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2022)
Article
Psychiatry
Parsa Ravanfar, Warda T. Syeda, Mahesh Jayaram, R. Jarrett Rushmore, Bradford Moffat, Alexander P. Lin, Amanda E. Lyall, Antonia H. Merritt, Negin Yaghmaie, Liliana Laskaris, Sandra Luza, Carlos M. Opazo, Benny Liberg, M. Mallar Chakravarty, Gabriel A. Devenyi, Patricia Desmond, Vanessa L. Cropley, Nikos Makris, Martha E. Shenton, Ashley Bush, Dennis Velakoulis, Christos Pantelis
Summary: This study found increased iron in the putamen in schizophrenia, as well as network-wide disturbances of iron and metabolic status.