Explanipedia

PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment Open

Yong Huang, Hidenori Homma, Xigui Chen, Hikari Tanaka, Kyota Fujita , et al. · 2025

High calorie-high fat diet (HFD) has been implicated as a pathological modifier of brain diseases including neurodegenerative dementias, but the detailed molecular mechanisms remain largely unknown. Here we report that HFD suppresses PPARγ…

Loss of function of VCP/TER94 causes neurodegeneration Open

Kohei Tsumaki, Christian J.F. Bertens, Minoru Nakayama, Shinsuke Kato, Yuki Jonao , et al. · 2024

Variants in several genes are linked to human frontotemporal lobar degeneration (FTLD) associated with TDP43- and/or ubiquitin-positive inclusions. However, it is not yet clear whether the underlying mechanism is a gain-of-function or a lo…

PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation Open

Yuki Yoshioka, Yong Huang, Xiaocen Jin, Kien Xuan Ngo, Tomohiro Kumaki , et al. · 2024

Senescence of nondividing neurons remains an immature concept, with especially the regulatory molecular mechanisms of senescence-like phenotypes and the role of proteins associated with neurodegenerative diseases in triggering neuronal sen…

PQBP3/NOL7 is an intrinsically disordered protein Open

Hidenori Homma, Kien Xuan Ngo, Yuki Yoshioka, Hikari Tanaka, Maiko Inotsume , et al. · 2024

PQBP3 is a protein binding to polyglutamine tract sequences that are expanded in a group of neurodegenerative diseases called polyglutamine diseases. The function of PQBP3 was revealed recently as an inhibitor protein of proteasome-depende…

Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage Open

Hidenori Homma, Yuki Yoshioka, Kyota Fujita, Shinichi Shirai, Yuka Hama , et al. · 2024

Better understanding of the earliest molecular pathologies of all neurodegenerative diseases is expected to improve human therapeutics. We investigated the earliest molecular pathology of spinocerebellar ataxia type 1 (SCA1), a rare famili…

Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease Open

Hidenori Homma, Hikari Tanaka, Kyota Fujita, Hitoshi Okazawa · 2024

The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death …

Complement Component C4a Shapes Prosociality via Binding of Oxytocin Open

Yasuhiko Yamamoto, Teruko Yuhi, Anpei Zhang, Ai Harashima, Anna A. Shabalova , et al. · 2024

AAV-mediated editing of PMP22 rescues Charcot-Marie-Tooth disease type 1A features in patient-derived iPS Schwann cells Open

Yuki Yoshioka, Juliana Bosso Taniguchi, Hidenori Homma, T. Tamura, Kyota Fujita , et al. · 2023

Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability Open

Terence Gall-Duncan, Jennifer Luo, Carla-Marie Jurkovic, Laura A. Fischer, Kyota Fujita , et al. · 2023

Mutant α-synuclein propagates via the lymphatic system of the brain in the monomeric state Open

Kyota Fujita, Hidenori Homma, Meihua Jin, Yuki Yoshioka, Xiaocen Jin , et al. · 2023

Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the in vivo propagation pattern and aggregation state of mutant α-synuclein by injecting adeno-associated viral (…

PQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions Open

Xiaocen Jin, Hikari Tanaka, Meihua Jin, Kyota Fujita, Hidenori Homma , et al. · 2023

Polyglutamine binding protein 5 (PQBP5), also called nucleolar protein 10 (NOL10), binds to polyglutamine tract sequences and is expressed in the nucleolus. Using dynamic imaging of high-speed atomic force microscopy, we show that PQBP5/NO…

Antagonistic roles of canonical and alternative RPA in tandem CAG repeat diseases Open

Terence Gall-Duncan, Jennifer Luo, Carla-Marie Jurkovic, Laura A. Fischer, Kyota Fujita , et al. · 2022

Tandem CAG repeat expansion mutations cause >15 neurodegenerative diseases, where ongoing expansions in patients’ brains are thought to drive disease onset and progression. Repeat length mutations will involve single-stranded DNAs prone to…

Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice Open

Hiroki Shiwaku, Shingo Katayama, Kanoh Kondo, Yuri Nakano, Hikari Tanaka , et al. · 2022

From genetic and etiological studies, autoimmune mechanisms underlying schizophrenia are suspected; however, the details remain unclear. In this study, we describe autoantibodies against neural cell adhesion molecule (NCAM1) in patients wi…

Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation Open

Meihua Jin, Hiroki Shiwaku, Hikari Tanaka, Takayuki Obita, Sakurako Ohuchi , et al. · 2021

Brain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins by direct interaction and triggers an in…

HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology Open

Hikari Tanaka, Kanoh Kondo, Kyota Fujita, Hidenori Homma, Kazuhiko Tagawa , et al. · 2021

DNA damage is increased in Alzheimer’s disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77…

Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis Open

Meihua Jin, Xiaocen Jin, Hidenori Homma, Kyota Fujita, Hikari Tanaka , et al. · 2021

DNA damage in embryonic neural stem cell determines FTLDs’ fate via early-stage neuronal necrosis Open

Hidenori Homma, Hikari Tanaka, Meihua Jin, Xiaocen Jin, Yong Huang , et al. · 2021

The early-stage pathologies of frontotemporal lobal degeneration (FTLD) remain largely unknown. In VCP T262A -KI mice carrying VCP gene mutation linked to FTLD, insufficient DNA damage repair in neural stem/progenitor cells (NSCs) activate…

Role of the Drosophila YATA protein in the proper subcellular localization of COPI revealed by in vivo analysis Open

Maiko Saito, Minoru Nakayama, Kyota Fujita, Atsuko Uchida, Hiroyuki Yano , et al. · 2020

yata mutants of Drosophila melanogaster exhibit phenotypes including progressive brain shrinkage, developmental abnormalities and shortened lifespan, whereas in mammals, null mutations of the yata ortholog Scyl1 result in motor neuron dege…

YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology Open

Hikari Tanaka, Hidenori Homma, Kyota Fujita, Kanoh Kondo, Shingo Yamada , et al. · 2020

PQBP1, an intellectual disability causative gene, affects bone development and growth Open

Shin-Sheng Yang, T Ishida, Kyota Fujita, Yuta Nakai, Takashi Ono , et al. · 2020

Polyglutamine tract-binding protein 1 (PQBP1), an intellectual disability causative gene, is involved in transcriptional and post-transcriptional regulation of gene expression in animals, and possibly also in plants. In our previous work, …

Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex Open

Seika Inoue, Kanehiro Hayashi, Kyota Fujita, Kazuhiko Tagawa, Hitoshi Okazawa , et al. · 2018

The actin cytoskeleton is crucial for neuronal migration in the mammalian developing cerebral cortex. The adaptor protein Drebrin-like (Dbnl) plays important roles in reorganization of the actin cytoskeleton, dendrite formation, and endocy…

The intellectual disability gene PQBP1 rescues Alzheimer’s disease pathology Open

Hikari Tanaka, Kanoh Kondo, Xigui Chen, Hidenori Homma, Kazuhiko Tagawa , et al. · 2018

Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology Open

Kyota Fujita, Hidenori Homma, Kanoh Kondo, Masashi Ikuno, Hodaka Yamakado , et al. · 2018

Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate …

Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology Open

Kyota Fujita, Xigui Chen, Hidenori Homma, Kazuhiko Tagawa, Mutsuki Amano , et al. · 2018

Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1 Open

Kyota Fujita, Yingwei Mao, Shigenori Uchida, Xigui Chen, Hiroki Shiwaku , et al. · 2017

A novel form of necrosis, TRIAD, occurs in human Huntington’s disease Open

Emiko Yamanishi, Kazuko Hasegawa, Kyota Fujita, Shizuko Ichinose, Saburo Yagishita , et al. · 2017

Identification of hepta-histidine as a candidate drug for Huntington’s disease by in silico-in vitro- in vivo-integrated screens of chemical libraries Open

Tomomi Imamura, Kyota Fujita, Kazuhiko Tagawa, Teikichi Ikura, Xigui Chen , et al. · 2016

Targeting TEAD/YAP-transcription-dependent necrosis, TRIAD, ameliorates Huntington’s disease pathology Open

Yingwei Mao, Xigui Chen, Min Xu, Kyota Fujita, Kazumi Motoki , et al. · 2016

Neuronal cell death in neurodegenerative diseases is not fully understood. Here we report that mutant huntingtin (Htt), a causative gene product of Huntington’s diseases (HD) selectively induces a new form of necrotic cell death, in which …

HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease Open

Kyota Fujita, Kazumi Motoki, Kazuhiko Tagawa, Xigui Chen, Hiroshi Hama , et al. · 2016

Alzheimer’s disease (AD) is the most common neurodegenerative disease, but it remains an intractable condition. Its pathogenesis is predominantly attributed to the aggregation and transmission of two molecules, Aβ and tau; however, other p…

RpA1 ameliorates symptoms of mutant ataxin-1 knock-in mice and enhances DNA damage repair Open

Juliana Bosso Taniguchi, Kanoh Kondo, Kyota Fujita, Xigui Chen, Hidenori Homma , et al. · 2016

DNA damage and repair is a critical domain of many neurodegenerative diseases. In this study, we focused on RpA1, a candidate key molecule in polyQ disease pathologies, and tested the therapeutic effect of adeno-associated virus (AAV) vect…

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