Article
Neurosciences
Brigid K. Jensen, Kevin J. McAvoy, Nicolette M. Heinsinger, Angelo C. Lepore, Hristelina Ilieva, Aaron R. Haeusler, Davide Trotti, Piera Pasinelli
Summary: Mutations in ubiquitously expressed genes are common in ALS, a motor neuron disease, and dysfunction of non-neuronal cells also contributes to the disease. This study demonstrates that a specific mutation in astrocytes induces neurotoxicity and death of spinal motor neurons through upregulation of TNF alpha. Targeting TNF alpha shows therapeutic success in preventing neurodegeneration and motor dysfunction.
Article
Genetics & Heredity
Jeremy T. T. Lant, Farah Hasan, Julia Briggs, Ilka U. U. Heinemann, Patrick O'Donoghue
Summary: High-fidelity protein synthesis relies on properly aminoacylated tRNAs, but cells have the ability to tolerate errors in translation due to mutations in tRNAs and other components. A mutant tRNA variant, tRNA(AAA)(Ser), was found in 2% of the human population and showed defective protein synthesis and degradation. In this study, we demonstrated that this tRNA variant enhanced the toxicity of ALS-associated protein aggregation, particularly with the ALS-causative FUS R521C variant, leading to cell rupture and synthetic toxicity in neuroblastoma cells.
Article
Biochemistry & Molecular Biology
Francesco De Nuccio, Marianna Kashyrina, Francesca Serinelli, Florent Laferriere, Dario Domenico Lofrumento, Francesca De Giorgi, Francois Ichas
Summary: alpha-Synucleinopathies are neurodegenerative disorders characterized by the accumulation of insoluble alpha-Synuclein fibrils. These fibrils can form Lewy bodies in somata and Lewy neurites in neuronal processes. In multiple system atrophy, alpha-Synuclein aggregates are found in mature oligodendrocytes, but the origin of these aggregates is still unknown.
Article
Neurosciences
Antonietta Notaro, Antonella Messina, Vincenzo La Bella
Summary: Mutations in the Fused-in-Sarcoma (FUS) gene can lead to ALS, with mislocalization of mutant FUS protein to stress granules possibly contributing to neurodegeneration. Stress-induced SGs containing mutant FUS tend to fail to dissolve after stress, promoting a liquid-to-solid phase transition. This could represent a potential target for future innovative therapies in ALS.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Hiroyuki Honda, Motoi Yoshimura, Hajime Arahata, Kaoru Yagita, Shoko Sadashima, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Hideko Noguchi, Naokazu Sasagasako
Summary: FUS mutations play a significant role in ALS-FUS and colocalize with other hnRNPs such as TDP43, PCBP2, and PCBP1, suggesting impaired RNA metabolism.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
Masahiro Nogami, Mitsuru Ishikawa, Atsushi Doi, Osamu Sano, Takefumi Sone, Tetsuya Akiyama, Masashi Aoki, Atsushi Nakanishi, Kazuhiro Ogi, Masato Yano, Hideyuki Okano
Summary: This study utilized a novel technology, iBRN, to analyze gene regulatory network based on induced pluripotent stem cell (iPSC)-derived cell model, revealing hub molecules like miR-125b-5p-TIMELESS axis and PRKDC for the molecular aetiology of neurodegenerative diseases. The research provided first compelling evidence to elucidate the molecular aetiology in ALS.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Immunology
Alexander Trofimov, Dmitrii Pavlov, Anand Goswami, Anna Gorlova, Kirill Chaprov, Aleksei Umriukhin, Allan Kalueff, Alexey Deykin, Klaus-Peter Lesch, Daniel Clive Anthony, Tatyana Strekalova
Summary: In transgenic mice, FUS mutations enhance inflammatory response, but have no lasting impact on disease progression.
BRAIN BEHAVIOR & IMMUNITY-HEALTH
(2023)
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)