Updated on 2022/01/27

写真a

 
TSUBOGUCHI Shintaro
 
Organization
University Medical and Dental Hospital Neurology Assistant Professor
Title
Assistant Professor
External link

Degree

  • 博士(医学) ( 2021.3 )

Research Interests

  • 筋萎縮性側索硬化症

Research History

  • Niigata University   University Medical and Dental Hospital   Assistant Professor

    2021.4

Education

 

Papers

  • Age-related demethylation of the TDP-43 autoregulatory region in the human motor cortex

    Yuka Koike, Akihiro Sugai, Norikazu Hara, Junko Ito, Akio Yokoseki, Tomohiko Ishihara, Takuma Yamagishi, Shintaro Tsuboguchi, Mari Tada, Takeshi Ikeuchi, Akiyoshi Kakita, Osamu Onodera

    2021.1

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    Publisher:Cold Spring Harbor Laboratory  

    <title>Abstract</title>In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43) forms aggregates in the motor cortex of the aging brain. This aggregate formation may be triggered by the increase in TDP-43 levels with aging. However, the amount of TDP-43 is autoregulated by the alternative splicing of the <italic>TARDBP</italic> 3’UTR, and its relationship with aging remains unresolved. Since DNA methylation is altered during aging, we hypothesized that 3’UTR methylation is also altered in the aging motor cortex, disrupting this autoregulatory system and increasing TDP-43 levels. We found that DNA demethylation in the autoregulatory region of TDP-43 reduced alternative splicing and increased TDP-43 expression. Furthermore, in the human motor cortex, we found that this region was demethylated with age and that the expression of TDP-43 increased. The dysregulation of TDP-43 autoregulation by age-related DNA demethylation in the motor cortex may explain the contribution of aging and system selectivity in ALS.

    DOI: 10.1101/2021.01.13.426599

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  • Intracortical and corticospinal spreading of TDP-43 in mouse FTLD/ALS models(和訳中)

    坪口 晋太朗, 中村 由香, 石原 智彦, 加藤 泰介, 小山 哲秀, 佐藤 時春, 吉田 富, 上野 将紀, 小野寺 理

    Dementia Japan   34 ( 4 )   524 - 524   2020.10

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    Language:English   Publisher:(一社)日本認知症学会  

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  • FTLD/ALSモデルマウスにおけるTDP-43の皮質内と皮質脊髄内での増殖(Intracortical and corticospinal spreading of TDP-43 in mouse FTLD/ALS models)

    坪口 晋太朗, 中村 由香, 石原 智彦, 加藤 泰介, 小山 哲秀, 佐藤 時春, 吉田 富, 上野 将紀, 小野寺 理

    Dementia Japan   34 ( 4 )   524 - 524   2020.10

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    Language:English   Publisher:(一社)日本認知症学会  

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  • Herpes simplex encephalitis presenting as stroke-like symptoms with atypical MRI findings and lacking cerebrospinal fluid pleocytosis Reviewed

    Shintaro Tsuboguchi, Takahiro Wakasugi, Yoshitaka Umeda, Maiko Umeda, Mutsuo Oyake, Nobuya Fujita

    Rinsho Shinkeigaku   57 ( 7 )   387 - 390   2017

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    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Publisher:Societas Neurologica Japonica  

    DOI: 10.5692/clinicalneurol.cn-001033

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  • A case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration successfully treated with antitumor and immunotherapy. Reviewed

    Shintaro Tsuboguchi, Ryuji Yajima, You Higuchi, Masanori Ishikawa, Izumi Kawachi, Yu Koyama, Masatoyo Nishizawa

    Rinsho shinkeigaku = Clinical neurology   56 ( 7 )   477 - 80   2016

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    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report a case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration (PCD) with breast cancer in a 54-year-old woman. The symptoms of limb and truncal ataxia, and dysarthria gradually progressed during the course of 1 year, and the modified Rankin scale (mRS) score was 2. A mastectomy with sentinel lymph node resection was performed for the breast cancer. No malignant cells were found on histopathological examination of the lymph node. Combination chemotherapy with adriamycin and cyclophosphamide (AC) prevented neurologic deterioration. However, subsequent treatment with trastuzumab and paclitaxel did not prevent progression of the symptoms (mRS score 3). Brain magnetic resonance imaging showed atrophy of the cerebellar hemispheres without brain stem atrophy. Anti-Yo antibody was detected in the serum, which led to a diagnosis of anti-Yo-associated PCD. We resected an enlarged axillary lymph node, which was found on computed tomography. The histopathological analysis of the lymph node revealed foreign body granuloma, which suggested an association with necrotic malignant tissue. Following additional tegafur-uracil therapy and two courses of intravenous immunoglobulin (IVIg), the cerebellar signs and symptoms gradually improved (mRS score 2). The clinical course shows that PCD can present as a slowly progressive cerebellar symptom. We propose an active treatment for anti-Yo-associated PCD consisting of tumor resection, combined chemotherapy, and IVIg.

    DOI: 10.5692/clinicalneurol.cn-000872

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  • 緩徐に進行する小脳症状を呈した54歳女性例

    坪口 晋太朗, 矢島 隆二, 樋口 陽, 石川 正典, 河内 泉, 小山 諭, 西澤 正豊

    臨床神経学   55 ( 1 )   64 - 64   2015.1

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    Language:Japanese   Publisher:(一社)日本神経学会  

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MISC

  • [Molecular Pathogenesis of Amyotrophic Lateral Sclerosis].

    Shintaro Tsuboguchi, Tomohiko Ishihara, Akihiro Sugai, Akio Yokoseki, Osamu Onodera

    Brain and nerve = Shinkei kenkyu no shinpo   71 ( 11 )   1183 - 1189   2019

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    Authorship:Lead author   Language:Japanese  

    The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) has been studied through analysis of the function of the protein produced by the causative genes of familial ALS. The products of these genes are classified as RNA binding proteins, or proteins related to proteolytic systems. However, most case of familial ALS, and sporadic ALS show TAR DNA binding protein-43 (TDP-43) immune-positive cytoplasmic inclusions. Therefore, the molecular mechanism of formation of TDP-43 inclusions and dysfunction caused by TDP-43 inclusions has been studied. As for the mechanism of inclusion formation, non-membrane organelle formation by liquid-liquid phase separation (LLPS) is important. The ubiquitin-proteasome and autophagy systems are important for the degradation of these inclusions. Several genes associated with these systems have been identified as causative genes for ALS. The formation of cytoplasmic inclusions results in the loss of TDP-43 from the nucleus, resulting in abnormalities in RNA metabolism, through the alteration of spliceosomes and Gemini of coiled bodies. Furthermore, in ALS, the regulation of TDP-43 mRNA/protein expression levels has failed. Failure of the autoregulation system facilitates TDP-43 inclusion formation. Development of treatments for ALS based on these elucidated molecular mechanisms is desirable.

    DOI: 10.11477/mf.1416201428

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  • Friedreich 失調症と鉄代謝

    Shintaro Tsuboguchi, Tomohiko Ishihara, Osamu Onodera

    Clinical Neuroscience   37 ( 3 )   308 - 310   2019

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    Authorship:Lead author   Language:Japanese  

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