2025/08/31 更新

写真a

アニシモフ セルゲイ
ANISIMOV SERGEI
ANISIMOV SERGEI
所属
教育研究院 医歯学系 特任助教
医歯学総合研究科 特任助教
職名
特任助教
外部リンク

学位

  • Ph.D. ( 2019年 )

  • Medical Doctor ( 2014年 )

研究キーワード

  • autophagy

  • neurodegeneration

  • virology

  • protein aggregations

研究分野

  • ライフサイエンス / 病態神経科学  / Parkinsons disease

  • ライフサイエンス / 細胞生物学  / Autophagy

経歴(researchmap)

  • Niigata University Graduate School of Medical and Dental Sciences   Virology Division   Postdoctoral researcher

    2019年 - 現在

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経歴

  • 新潟大学   教育研究院 医歯学系   特任助教

    2023年4月 - 現在

  • 新潟大学   医歯学総合研究科   特任助教

    2020年7月 - 現在

  • 新潟大学   教育研究院 医歯学系   特任助教

    2020年7月 - 2022年5月

  • 新潟大学   医歯学総合研究科   特任助手

    2019年10月 - 2020年6月

学歴

  • 新潟大学   Graduate School of Medical and Dental Sciences, Virology Division   Ph.D. course

    2015年10月 - 2019年9月

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  • Krasnoyarsk State Medical University   Faculty of General Medicine   General Medicine

    2009年9月 - 2015年6月

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所属学協会

 

論文

  • USP10 inhibits the degradation of α-synuclein, a pathogenic factor associated with Parkinson's disease, by inhibiting chaperone-mediated autophagy. 国際誌

    Sergei Anisimov, Masahiko Takahashi, Taichi Kakihana, Yoshinori Katsuragi, Junya Sango, Takayuki Abe, Masahiro Fujii

    The Journal of biological chemistry   301 ( 7 )   110292 - 110292   2025年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, particularly in the substantia nigra of the brain. α-Synuclein is a major causative factor in both familial and sporadic forms of PD, and its protein aggregates play critical roles in neuronal cell death and PD pathogenesis. This study explored the role of ubiquitin-specific protease 10 (USP10) in the regulation of α-synuclein in neuronal cells. Knockdown of USP10 in SH-SY5Y neuronal cells led to a reduction in α-synuclein levels, which was reversed by inhibiting chaperone-mediated autophagy (CMA) through lysosome-associated membrane protein 2A depletion, a protein essential for CMA. A novel CMA reporter with a specific CMA degradation motif further demonstrated that knockdown of USP10 activated CMA in neuronal cells. In addition, USP10 overexpression increased the levels of both WT and five PD-associated α-synuclein mutants, whereas a deubiquitinase-deficient USP10 mutant did not increase α-synuclein levels. This study provides new insights into the mechanisms that regulate α-synuclein proteostasis and highlights USP10 as a promising drug target for PD.

    DOI: 10.1016/j.jbc.2025.110292

    PubMed

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  • Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry. 国際誌

    Kanako Watanabe, Tomoichiro Oka, Hirotaka Takagi, Sergei Anisimov, Shun-Ichi Yamashita, Yoshinori Katsuragi, Masahiko Takahashi, Masaya Higuchi, Tomotake Kanki, Akihiko Saitoh, Masahiro Fujii

    Nature communications   14 ( 1 )   1817 - 1817   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

    DOI: 10.1038/s41467-023-37399-8

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    その他リンク: https://www.nature.com/articles/s41467-023-37399-8

  • USP10 inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity. 国際誌

    Junya Sango, Taichi Kakihana, Masahiko Takahashi, Yoshinori Katsuragi, Sergei Anisimov, Masaaki Komatsu, Masahiro Fujii

    The Journal of biological chemistry   298 ( 1 )   101448 - 101448   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Nrf2 is an antioxidant transcriptional activator in many types of cells, and its dysfunction plays key roles in a variety of human disorders, including Parkinson's disease (PD). PD is characterized by the selective loss of dopaminergic neurons in PD-affected brain regions. Dopamine treatment of neuronal cells stimulates the production of reactive oxygen species (ROS) and increases ROS-dependent neuronal apoptosis. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Taken together, these results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including PD.

    DOI: 10.1016/j.jbc.2021.101448

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  • G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10. 査読 国際誌

    Sergei Anisimov, Masahiko Takahashi, Taichi Kakihana, Yoshinori Katsuragi, Hiroki Kitaura, Lu Zhang, Akiyoshi Kakita, Masahiro Fujii

    Scientific reports   9 ( 1 )   12896 - 12896   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The aberrant accumulation of ubiquitinated protein aggregates in cells plays a critical role in the pathogenesis of several degenerative diseases, including Parkinson disease (PD) and cystic fibrosis (CF). In this study, we found that Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits ubiquitinated protein aggregations induced by p62 and USP10 in cultured cells. p62 is a ubiquitin receptor, and p62 and its binding partner USP10 have been shown to augment ubiquitinated protein aggregation. G3BP1 interacted with p62 and USP10 and inhibited p62/USP10-induced protein aggregation. The G3BP1 inhibition of protein aggregations targeted two aggregation-prone proteins, α-synuclein and CFTR-ΔF508, which are causative factors of PD and CF, respectively. G3BP1 depletion increased the amounts of ubiquitinated α-synuclein and CFTR-ΔF508 protein. A proteasome reporter indicated that G3BP1 depletion inhibits the proteasome activity. We herein present evidence that G3BP1, p62 and USP10 together control ubiquitinated protein toxicity by controlling both ubiquitination and aggregation. Taken together, these results suggest that G3BP1, p62 and USP10 could be therapeutic targets for ubiquitinated protein aggregation disorders, including PD and CF.

    DOI: 10.1038/s41598-019-46237-1

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  • USP10はアグリソームの形成を誘導し、ユビキチン化蛋白質オリゴマーの細胞毒性を抑制する

    高橋雅彦, Piatnitskaia Svetlana, Anisimov Sergei, 藤井雅寛

    新潟医学会雑誌   133 ( 4 )   2019年4月

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    記述言語:日本語  

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共同研究・競争的資金等の研究

  • Inactivation mechanism of alpha-synuclein oligomer toxicity in Parkinson's disease

    研究課題/領域番号:22K15377

    2022年4月 - 2024年3月

    制度名:科学研究費助成事業

    研究種目:若手研究

    提供機関:日本学術振興会

    アニシモフ セルゲイ

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

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