Article
Veterinary Sciences
Saki Nomura, Yui Kobatake, Satoshi Takashima, Hiroaki Kamishina, Makoto Urushitani, Naohito Nishii
Summary: Canine degenerative myelopathy (DM) is a progressive neurodegenerative disorder commonly associated with a specific mutation in the SOD1 gene. This study investigates the role of MIF in inhibiting the misfolding and accumulation of mutant SOD1 in DM. The results suggest that MIF can regulate the accumulation of SOD1 aggregates through its chaperone activity. Enhancing intracellular MIF chaperone activity may be an effective therapeutic strategy for DM.
RESEARCH IN VETERINARY SCIENCE
(2022)
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
Biochemistry & Molecular Biology
Akhtar Atiya, Abdullatif Bin Muhsinah, Mohammed Alrouji, Fahad A. Alhumaydhi, Waleed Al Abdulmonem, Mohammad A. Aljasir, Sharaf E. Sharaf, Mohammad Furkan, Rizwan Hasan Khan, Moyad Shahwan, Anas Shamsi
Summary: In this study, compounds with structural similarity to LCS-1 were screened and analyzed for their interaction with SOD1. Two potential SOD1 inhibitors were identified for further exploration.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Kento Wakayama, Shintaro Kimura, Yui Kobatake, Hiroaki Kamishina, Naohito Nishii, Satoshi Takashima, Ryo Honda, Yuji O. O. Kamatari
Summary: Canine degenerative myelopathy (DM) is a neurodegenerative disease that serves as a natural model for human amyotrophic lateral sclerosis (ALS). The aggregation of canine superoxide dismutase 1 (cSOD1) plays a key role in DM, similar to human ALS. The E40K mutation in cSOD1 is a major cause of DM.
Article
Chemistry, Physical
Meena Kumari, Shilpa Sharma, Shashank Deep
Summary: Protein aggregation plays a critical role in various biological and industrial processes. This study focuses on the inhibitory effect of ammonium and choline based ionic liquids (ILs) on the amyloid aggregation of human Cu-Zn superoxide dismutase (SOD1), a protein associated with amyotrophic lateral sclerosis (ALS). The results show that certain ILs effectively inhibit SOD1 fibrillation, while others have a dual effect of acting as an amyloid inhibitor at lower concentrations and a promoter at higher concentrations. The study also provides insights into the structural and functional role of ILs in stabilizing specific loop regions of SOD1.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biology
Stepan Timr, Fabio Sterpone
Summary: To prevent toxic aggregation caused by protein destabilization, this study investigates a mutant model of superoxide dismutase 1 through constructing protein models and using advanced computational techniques. The research shows that computational methods can describe the biochemical model features but also highlights the limitations of this approach in studying pathological mutants of the superoxide dismutase 1 protein.
Review
Pharmacology & Pharmacy
Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du
Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.
PHARMACOLOGICAL RESEARCH
(2021)
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
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
Biochemistry & Molecular Biology
Meenakshi Sundaram Kumar, Megan E. Fowler-Magaw, Daniel Kulick, Sivakumar Boopathy, Del Hayden Gadd, Melissa Rotunno, Catherine Douthwright, Diane Golebiowski, Issa Yusuf, Zuoshang Xu, Robert H. H. Brown Jr, Miguel Sena-Esteves, Alison L. O'Neil, Daryl A. Bosco
Summary: ALS-linked mutations can cause aberrant conformations in the SOD1 protein, and this study aimed to develop anti-SOD1 nanobodies that specifically target mutant and misfolded forms of SOD1. The researchers found that these nanobodies can stabilize mutant SOD1, enhance its expression, and restore its subcellular localization. In addition, the nanobodies promote neurite outgrowth in human motor neurons harboring the SOD1 A4V mutation and exhibit selectivity for human mutant SOD1 over mouse SOD1 in vitro, supporting their potential for preclinical testing in animal models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
Medicine, Research & Experimental
Min Kyung Park, Jun Ji, Keeok Haam, Tae-Hee Han, Seona Lim, Mi-Jung Kang, Soon Sung Lim, Hyun Seung Ban
Summary: Licochalcone A, a component of Glycyrrhiza uralensis, demonstrates potential as a therapeutic agent in hypoxic cancer cells by inhibiting HIF-1 alpha accumulation and mitochondrial respiration, leading to increased oxygen content and suppression of cancer cell viability.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu
Summary: Cardiovascular diseases are the leading cause of death worldwide, and hypoxia-inducible factors (HIFs) play an important role in their pathogenesis. Recent studies have revealed the role of cell-specific HIFs in various cardiovascular diseases, but the potential clinical application of HIF inhibitors in the treatment of cardiovascular diseases is not well understood.
PHARMACOLOGY & THERAPEUTICS
(2022)
Meeting Abstract
Clinical Neurology
Koji Tanaka, Shoji Matsumoto, Gulibahaer Ainiding, Ichiro Nakahara, Akira Ishii, Taketo Hatano, Kyoko Iinuma, Takuya Matsushita, Noriko Ishobe, Ryo Yamasaki, Izumi Nagata, Jun-Ichi Kira
Article
Immunology
Ban-yu Saitoh, Eizo Tanaka, Norio Yamamoto, Daan van Kruining, Kyoko Iinuma, Yuko Nakamuta, Hiroo Yamaguchi, Ryo Yamasaki, Koichiro Matsumoto, Jun-ichi Kira
Summary: Research findings suggest that early postnatal allergic airway inflammation induces gene expression changes that may affect microglial synaptic pruning function, leading to excitatory postsynaptic surplus and ASD-like behavior.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Immunology
Hayato Une, Ryo Yamasaki, Satoshi Nagata, Hiroo Yamaguchi, Yuko Nakamuta, Ulfa Camelia Indiasari, Yiwen Cui, Koji Shinoda, Katsuhisa Masaki, Magdalena Goetz, Jun-ichi Kira
Summary: By knocking out the Cx43 gene in astroglia, EAE clinical symptoms can be alleviated, reducing inflammation cell infiltration and demyelination in the spinal cord, meanwhile promoting anti-inflammatory gene expression and inhibiting proinflammatory gene expression.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Yuri Mizuno, Nona Abolhassani, Guianfranco Mazzei, Takashi Saito, Takaomi C. Saido, Ryo Yamasaki, Jun-ichi Kira, Yusaku Nakabeppu
Summary: Oxidative stress is a major risk factor for Alzheimer's disease, characterized by the accumulation of 8-oxoG in the brain. Deficiency of MTH1 and OGG1 accelerates the accumulation of 8-oxoG in DNA and leads to reduced anxiety-related behavior in 6-month-old mice.
NEUROSCIENCE RESEARCH
(2022)
Editorial Material
Clinical Neurology
Hajime Takeuchi, Katsuhisa Masaki, Hidenori Ogata, Satoshi Nagata, Takafumi Shimogawa, Ryo Yamasaki, Noriko Isobe
Article
Endocrinology & Metabolism
Muneo Yamaguchi, Shintaro Nakao, Iori Wada, Tetsuya Matoba, Mitsuru Arima, Yoshihiro Kaizu, Mariko Shirane, Keijiro Ishikawa, Takahito Nakama, Yusuke Murakami, Masaharu Mizuochi, Wataru Shiraishi, Ryo Yamasaki, Toshio Hisatomi, Tatsuro Ishibashi, Masabumi Shibuya, Alan W. Stitt, Koh-Hei Sonoda
Summary: In this study, it was found that there is a significant increase in intraretinal hyperreflective foci (HRF) in diabetic retinopathy (DR). The proliferation of vitreous resident macrophages (VRMs) at the vitreoretinal interface (VRI) is driven by vascular endothelial growth factor (VEGF), leading to the formation of HRF lesions. Anti-VEGF therapy can reverse this phenomenon.
Article
Clinical Neurology
Yuko Kobayakawa, Koji Todaka, Yu Hashimoto, Senri Ko, Wataru Shiraishi, Junji Kishimoto, Jun-ichi Kira, Ryo Yamasaki, Noriko Isobe
Summary: The study developed a new indicator, FVC-DiP, to assess disease progression rate in ALS. This indicator reflected disease progression patterns through %FVC decline, and showed associations with prognosis and TRICALS risk profile.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Tomoki Uchikawa, Tetsuya Matoba, Takuro Kawahara, Isashi Baba, Shunsuke Katsuki, Jun-ichiro Koga, Yu Hashimoto, Ryo Yamasaki, Ikuyo Ichi, Hidetaka Akita, Hiroyuki Tsutsui
Summary: Emerging evidence suggests that dietary intake of 7-ketocholesterol (7-KC) can cause inflammation and cardiovascular diseases. This study investigated the effects of dietary 7-KC on myocardial ischemia-reperfusion (IR) injury and identified the molecular mechanisms involved. The findings demonstrate that dietary 7-KC exacerbates myocardial IR injury through monocyte/macrophage-mediated inflammation, and that endoplasmic reticulum stress and oxidative stress play a role in the proinflammatory response induced by 7-KC in macrophages.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Kazunori Iwao, Mitsuru Watanabe, Takahiko Mukaino, Takayuki Fujii, Ryo Yamasaki, Noriko Isobe
Summary: This case study reports on a 30-year-old woman who presented with psychological symptoms and was later diagnosed with anti-NMDAR encephalitis and chromosomally integrated human herpesvirus 6 (ciHHV6). The patient had an ovarian teratoma, anti-NMDAR antibodies, and HHV6-DNA in her serum and cerebrospinal fluid. Treatment with laparoscopic oophorectomy and immunotherapy improved her symptoms and HHV6-DNA was detected in her oral mucosa cells. This case highlights the importance of differentiating between HHV6 infection and ciHHV6 when HHV6-DNA is detected in the cerebrospinal fluid of encephalitis patients.
NEUROLOGY AND CLINICAL NEUROSCIENCE
(2023)
Article
Clinical Neurology
Yuji Nishimura, Katsuhisa Masaki, Dai Matsuse, Hiroo Yamaguchi, Tatsunori Tanaka, Eriko Matsuo, Shotaro Hayashida, Mitsuru Watanabe, Takuya Matsushita, Shoko Sadashima, Naokazu Sasagasako, Ryo Yamasaki, Noriko Isobe, Toru Iwaki, Jun-Ichi Kira
Summary: The pathological hallmark of multiple system atrophy (MSA) is the accumulation of phosphorylated alpha-synuclein in oligodendrocytes, which leads to glial cytoplasmic inclusions. This study investigated the changes in glial connexins (Cxs) in MSA patients and found early and extensive alterations in Cx32, which may contribute to the demyelination and dysfunction in MSA.
Meeting Abstract
Clinical Neurology
Jun-ichi Kira, Hiroo Yamaguchi, Yuji Nishimura, Dai Matsuse, Katsuhisa Masaki, Ryo Yamasaki, Noriko Isobe
ANNALS OF NEUROLOGY
(2022)
Meeting Abstract
Environmental Sciences
Nona Abolhassani, Yuri Mizuno, Guianfranco Mazzei, Kunihiko Sakumi, Takashi Saito, Takaomi C. Saido, Toshiharu Ninomiya, Toru Iwaki, Ryo Yamasaki, Jun-Ichi Kira, Yusaku Nakabeppu
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Meeting Abstract
Clinical Neurology
Masahiro Iijima, Shinobu Shimizu, Yuki Fukami, Haruki Koike, Kenichi Kaida, Masahiro Mori, Satoshi Kuwabara, Michiaki Koga, Takashi Kanda, Hidenori Ogata, Ryo Yamasaki, Jun-ichi Kira, Masahisa Katsuno
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Meeting Abstract
Clinical Neurology
Hidenori Ogata, Yuko Kobayakawa, Abdelhadi Amina, Ryo Yamasaki, Atsushi Kawasaki, Chieri Takeuchi, Jun-ichi Kira, Noriko Isobe
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Meeting Abstract
Clinical Neurology
Xu Zhang, Hidenori Ogata, Tomohiro Imamura, Takayuki Fujii, Ryo Yamasaki, Jun-Ichi Kira
ANNALS OF NEUROLOGY
(2021)