2024/05/20 更新

写真a

マツモト ゲン
松本 弦
MATSUMOTO GEN
担当
大学院医学研究科 基礎医科学専攻 准教授
医学部 医学科
職名
准教授
所属
医学研究院

担当・職階

  • 大学院医学研究科 基礎医科学専攻 

    准教授  2024年04月 - 継続中

  • 医学部 医学科 

    准教授  2024年04月 - 継続中

取得学位

  • 博士(理学) ( 京都大学 )

研究分野

  • ライフサイエンス / 神経形態学

  • ライフサイエンス / 病態神経科学

  • ライフサイエンス / 分子生物学

研究キーワード

  • 選択的オートファジー

  • 神経変性疾患

  • 包括脳ネットワーク

  • リン酸化

  • ライブセルイメージング

  • オートファジーレセプター

  • アグリソーム

  • p62

所属学協会

  • 日本解剖学会

    2014年09月 - 継続中

  • 日本神経科学会

    2014年04月 - 継続中

  • 日本細胞生物学会

  • 日本分子生物学会

職務経歴(学外)

  • 大阪公立大学   医学研究科 基礎医科学専攻

    2024年04月 - 継続中

  • 国立研究開発法人量子科学技術研究開発機構   量子医学研究所 脳機能イメージング研究部   協力研究員

    2023年04月 - 継続中

  • 順天堂大学   寄附講座シヌクレイノパチー創薬探索研究講座   非常勤講師

    2021年07月 - 継続中

  • 長崎大学大学院   医歯薬学総合研究科

    2014年09月 - 2024年03月

論文

  • α-Synuclein: A Promising Biomarker for Parkinson's Disease and Related Disorders.

    Taku Hatano, Ayami Okuzumi, Gen Matsumoto, Tsunemi Taiji, Nobutaka Hattori

    Journal of movement disorders   2024年04月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson's disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.

    DOI: 10.14802/jmd.24075

    PubMed

  • Application of single-molecule analysis to singularity phenomenon of cells

    Hiroshima Michio, Bannai Hiroko, Matsumoto Gen, Ueda Masahiro

    Biophysics and Physicobiology   advpub ( 0 )   2024年

     詳細を見る

    <p>Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.</p>

    DOI: 10.2142/biophysico.bppb-v21.s018

  • Research on the molecular mechanism of singularity phenomenon in neurological disorders 査読

    Hiroko Bannai, Akihiko Takashima, Yoshiyuki Soeda, Hideaki Yoshimura, Gen Matsumoto, Naruhiko Sahara, Michio Hiroshima, Mitsuru Hattori, Takeharu Nagai

    Biophysics and Physicobiology   2024年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.2142/biophysico.bppb-v21.s008

  • α-シヌクレインシードの伝播凝集メカニズム

    奥住 文美, 波田野 琢, 松本 弦, 服部 信孝

    神経治療学   40 ( 6 )   S254 - S254   2023年10月( ISSN:0916-8443

  • The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. 査読

    Atsushi Hatanaka, Sota Nakada, Gen Matsumoto, Katsuya Satoh, Iori Aketa, Akira Watanabe, Tomoaki Hirakawa, Tadayuki Tsujita, Tsuyoshi Waku, Akira Kobayashi

    Scientific reports   13 ( 1 )   14405 - 14405   2023年09月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    The ubiquitin‒proteasome system (UPS) and autophagy are the two primary cellular pathways of misfolded or damaged protein degradation that maintain cellular proteostasis. When the proteasome is dysfunctional, cells compensate for impaired protein clearance by activating aggrephagy, a type of selective autophagy, to eliminate ubiquitinated protein aggregates; however, the molecular mechanisms by which impaired proteasome function activates aggrephagy remain poorly understood. Here, we demonstrate that activation of aggrephagy is transcriptionally induced by the transcription factor NRF1 (NFE2L1) in response to proteasome dysfunction. Although NRF1 has been previously shown to induce the expression of proteasome genes after proteasome inhibition (i.e., the proteasome bounce-back response), our genome-wide transcriptome analyses identified autophagy-related p62/SQSTM1 and GABARAPL1 as genes directly targeted by NRF1. Intriguingly, NRF1 was also found to be indispensable for the formation of p62-positive puncta and their colocalization with ULK1 and TBK1, which play roles in p62 activation via phosphorylation. Consistently, NRF1 knockdown substantially reduced the phosphorylation rate of Ser403 in p62. Finally, NRF1 selectively upregulated the expression of GABARAPL1, an ATG8 family gene, to induce the clearance of ubiquitinated proteins. Our findings highlight the discovery of an activation mechanism underlying NRF1-mediated aggrephagy through gene regulation when proteasome activity is impaired.

    DOI: 10.1038/s41598-023-41492-9

    PubMed

  • Propagative α-synuclein seeds as serum biomarkers for synucleinopathies. 査読

    Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-Ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gérardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori

    Nature medicine   29 ( 6 )   1448 - 1455   2023年06月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95-0.99)/AUC: 0.93 (95% CI 0.84-1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49-0.79)/AUC: 0.73 (95% CI 0.49-0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74-0.99)) and MSA (AUC: 0.80 (95% CI 0.65-0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.

    DOI: 10.1038/s41591-023-02358-9

    PubMed

  • IP/RT-QuICによるシヌクレノパチー疾患特異的血液アルファシヌクレインシードの検出

    奥住 文美, 波田野 琢, 松本 弦, 貫名 信行, 服部 信孝

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   16回   76 - 76   2022年07月

  • Detection of Prions in a Cadaver for Anatomical Practice.

    Takehiro Nakagaki, Miho Kaneko, Katsuya Satoh, Kiyohito Murai, Kazunobu Saiki, Gen Matsumoto, Keiko Ogami-Takamura, Kazuya Ikematsu, Akio Akagi, Yasushi Iwasaki, Toshiyuki Tsurumoto, Noriyuki Nishida

    The New England journal of medicine   386 ( 23 )   2245 - 2246   2022年06月

     詳細を見る

    国際・国内誌:国際誌  

    DOI: 10.1056/NEJMc2204116

    PubMed

  • Central role for p62/SQSTM1 in the elimination of toxic tau species in a mouse model of tauopathy. 査読

    Maiko Ono, Masaaki Komatsu, Bin Ji, Yuhei Takado, Masafumi Shimojo, Takeharu Minamihisamatsu, Eiji Warabi, Toru Yanagawa, Gen Matsumoto, Ichio Aoki, Nicholas M Kanaan, Tetsuya Suhara, Naruhiko Sahara, Makoto Higuchi

    Aging cell   21 ( 7 )   e13615   2022年06月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   国際・国内誌:国際誌  

    Intracellular accumulation of filamentous tau aggregates with progressive neuronal loss is a common characteristic of tauopathies. Although the neurodegenerative mechanism of tau-associated pathology remains unclear, molecular elements capable of degrading and/or sequestering neurotoxic tau species may suppress neurodegenerative progression. Here, we provide evidence that p62/SQSTM1, a ubiquitinated cargo receptor for selective autophagy, acts protectively against neuronal death and neuroinflammation provoked by abnormal tau accumulation. P301S mutant tau transgenic mice (line PS19) exhibited accumulation of neurofibrillary tangles with localization of p62 mostly in the brainstem, but neuronal loss with few neurofibrillary tangles in the hippocampus. In the hippocampus of PS19 mice, the p62 level was lower compared to the brainstem, and punctate accumulation of phosphorylated tau unaccompanied by co-localization of p62 was observed. In PS19 mice deficient in p62 (PS19/p62-KO), increased accumulation of phosphorylated tau, acceleration of neuronal loss, and exacerbation of neuroinflammation were observed in the hippocampus as compared with PS19 mice. In addition, increase of abnormal tau and neuroinflammation were observed in the brainstem of PS19/p62-KO. Immunostaining and dot-blot analysis with an antibody selectively recognizing tau dimers and higher-order oligomers revealed that oligomeric tau species in PS19/p62-KO mice were significantly accumulated as compared to PS19 mice, suggesting the requirement of p62 to eliminate disease-related oligomeric tau species. Our findings indicated that p62 exerts neuroprotection against tau pathologies by eliminating neurotoxic tau species, suggesting that the manipulative p62 and selective autophagy may provide an intrinsic therapy for the treatment of tauopathy.

    DOI: 10.1111/acel.13615

    PubMed

  • IP/RT-QuICによるシヌクレノパチー疾患特異的血液アルファシヌクレインシードの検出

    奥住 文美, 波田野 琢, 松本 弦, 貫名 信行, 服部 信孝

    日本内科学会雑誌   111 ( Suppl. )   207 - 207   2022年02月( ISSN:0021-5384

  • Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's disease patients 査読

    Miwako Kawamura, Shigeto Sato, Gen Matsumoto, Takahiro Fukuda, Kahori Shiba-Fukushima, Sachiko Noda, Masashi Takanashi, Nozomu Mori, Nobutaka Hattori

    Neuroscience Letters   699   59 - 63   2019年04月( ISSN:0304-3940

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    © 2019 The Authors Parkinson's disease (PD) is the second most common neurodegenerative disease. Lewy bodies and pale bodies in dopaminergic neurons in the substantia nigra are pathological hallmarks of PD. A number of neurodegenerative diseases demonstrate aggregate formation, but how these aggregates are associated with their pathogenesis remains unknown. It has been reported that repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is induced in the nuclei of aged neurons, preserves neuronal function, and protects against neurodegeneration during aging through the repression of cell death-inducing genes. The loss of REST is associated with Alzheimer's disease pathology. However, its function in dopaminergic neurons remains unknown. Here we demonstrated that REST enters the nucleus of aged dopaminergic neurons. On the other hand, REST is partially sequestrated in Lewy bodies and is mostly absent from the nucleus of neurons in brains with PD and dementia with Lewy bodies (DLB). Dopaminergic neuron-specific autophagy-deficient mice exhibit REST accumulation in aggregates. Defects in the protein quality control system induce REST mRNA expression; its gene product mainly appears in aggregates. Our results suggest that Lewy pathology disturbs normal aging processes in dopaminergic neurons by sequestering REST and the loss of REST may associate with the PD pathology.

    DOI: 10.1016/j.neulet.2019.01.042

    PubMed

▼全件表示

書籍等出版物

MISC(その他記事)

  • Propagative α-synuclein seeds as serum biomarkers for synucleinopathies.

    Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-Ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gérardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori

    Nature medicine   29 ( 6 )   1448 - 1455   2023年05月

     詳細を見る

    Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95-0.99)/AUC: 0.93 (95% CI 0.84-1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49-0.79)/AUC: 0.73 (95% CI 0.49-0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74-0.99)) and MSA (AUC: 0.80 (95% CI 0.65-0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.

    DOI: 10.1038/s41591-023-02358-9

    PubMed

  • α-シヌクレインシードの伝播凝集メカニズム

    奥住文美, 波田野琢, 松本弦, 服部信孝, 服部信孝

    神経治療学(Web)   40 ( 6 )   2023年( ISSN:2189-7824

     詳細を見る

  • 組織中における管腔走行の可視化を目的とした組織透明化法の検討

    村井清人, 佐伯和信, 遠藤大輔, 遠藤大輔, 高村敬子, 高村敬子, 松本弦, 田口紘平, 弦本敏行, 弦本敏行

    日本解剖学会総会・全国学術集会抄録集(CD-ROM)   128th   2023年

     詳細を見る

  • 線維化タウ凝集体細胞モデルと認知症研究 招待

    松本 弦

    コスモバイオニュース   168   1 - 3   2020年11月

     詳細を見る

    担当区分:筆頭著者, 最終著者, 責任著者   掲載種別:記事・総説・解説・論説等(その他)  

講演・口頭発表等

▼全件表示

産業財産権等

  • タンパク質凝集体の分解促進用組成物、およびタンパク質凝集体形成

    松本 弦, 水田賢志

     詳細を見る

    産業財産権の種類:特許権 

    出願番号:特願2023-030021 

  • パーキンソン病と多系統萎縮症の鑑別診断

    服部 信孝, 波田野 琢, 奥住 文美, 松本 弦

     詳細を見る

    産業財産権の種類:特許権 

    出願番号:特願2021-000188 

    公開番号:特開2022-105412 

    J-GLOBAL

  • パーキンソン病と多系統萎縮症の鑑別診断

    服部信孝, 波田野琢, 奥住文美, 松本弦

     詳細を見る

    産業財産権の種類:特許権 

    出願番号:特願2021-000188 

学外での担当授業科目

  • 発生・組織学実習

    2019年06月
    -
    継続中
    機関名:長崎大学医学部

  • 神経・感覚器系

    2018年
    -
    継続中
    機関名:長崎大学医学部

  • リサーチセミナー

    2014年09月
    -
    継続中
    機関名:長崎大学医学部

  • 神経解剖学実習

    2014年09月
    -
    継続中
    機関名:長崎大学医学部