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研究テーマ	遺伝性パーキンソン病の病理メカニズムの解明
研究業績（論文）	1. Inoshita T, Liu J-Y, Taniguchi D, Ishii R, Shiba-Fukushima K, Hattori N, Imai Y: Parkinson’s disease-associated Leucine-rich repeat kinase regulates UNC-104-dependent axonal transport of Arl8-positive vesicles in Drosophila. iScience 25, 105476 (2022) 2. Tezuka T, Taniguchi D, Sano M, Shimada T, Oji Y, Tsunemi T, Ikeda A, Li Y, Yoshino H, Ogata J, Shiba-Fukushima K Funayama M, Nishioka K, Imai Y†, Hattori N†: Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson’s disease. NPJ Parkinsons Dis. 8, Article number: 97 (2022) 3. Daida K, Shimonaka S, Shiba-Fukushima K, Ogata J, Yoshino H, Okuzumi A, Hatano T, Motoi Y, Hirunagi T, Katsuno M, Shindou H, Funayama M, Nishioka K, Hattori N, Imai Y: α-Synuclein V15A variant in familial Parkinson's disease exhibits a weaker lipid-binding property. Mov Disord. 37, 2075-2085 (2022) 4. Liu J-Y, Inoshita T, Shiba-Fukushima K, Yoshida S, Ogata K, Ishihama Y, Imai Y†, Hattori N†: Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation. Hum Mol Genet. 31:2623-2638 (2022) 5. Liu J-Y, Inoshita T, Shiba-Fukushima K, Yoshida S, Ogata K, Ishihama Y, Imai Y, Hattori N: Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation. Hum Mol Genet. (2022) in press 6. Kato S, Arasaki K, Tokutomi N, Imai Y, Inoshita T, Hattori N, Sasaki T, Sato M, Wakana Y, Inoue H, Tagaya M: Syntaxin 17, an ancient SNARE paralog, plays different and conserved roles in different organisms. J Cell Sci. 134: jcs258699 (2021) 7. Hung YC, Huang KL, Chen PL, Li JL, Lu SH, Chang JC, Lin HY, Lo WC, Huang SY, Lee TT, Lin TY, Imai Y, Hattori N, Liu CS, Tsai SY, Chen CH, Lin CH, Chan CC: UQCRC1 engages cytochrome c for neuronal apoptotic cell death. Cell Rep. 36: 109729 (2021) 8. Elahi M, Motoi Y, Shimonaka S, Ishida Y, Hioki H, Takanashi M, Ishiguro K, Imai Y, Hattori N: High-fat diet-induced activation of SGK1 promotes Alzheimer's disease-associated tau pathology. Hum Mol Genet. 30: 1693-1710 (2021) 9. Ogata J, Hirao K, Nishioka K, Hayashida A, Li Y, Yoshino H, Shimizu S, Hattori N, Imai Y: A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels. Int. J. Mol. Sci. 22: 3708 (2021) 10. Kano M, Takanashi M, Oyama G, Yoritaka A, Hatano T, Shiba-Fukushima K, Nagai M, Nishiyama K, Hasegawa K, Inoshita T, Ishikawa K-i, Akamatsu W, Imai Y, Bolognin S, Schwamborn JC, Hattori N: Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinsons Dis 6: Article number 33 (2020) 11. Masuzugawa S, Nishioka K, Imai Y, Ogata J, Shojima Y, Li Y, Yoshino H, Hattori N: A novel rare variant of LRRK2 associated with familial Parkinson's disease: p.R1501W. Parkinsonism Relat Disord 76:46-48 (2020) 12. Yamaguchi A, Ishikawa K-I, Inoshita T, Shiba-Fukushima K, Saiki S, Hatano T, Mori A, Oji Y, Okuzumi A, Li Y, Funayama M, Imai Y, Hattori N, Akamatsu W: Identifying therapeutic agents for amelioration of mitochondrial clearance disorder in neurons of familial Parkinson's disease. Stem Cell Reports. 14: 1060-1075 (2020) 13. Shiba-Fukushima K, Inoshita T, Sano O, Iwata H, Ishikawa K-i, Okano H, Akamatsu W, Imai Y, Hattori N: A cell-based high-throughput screening identified two compounds that enhance PINK1-Parkin signaling. iScience. Article number: 101048 (2020) 14. Imai Y, Inoshita T, Meng H, Shiba-Fukushima K, Hara KY, Sawamura N, Hattori N: Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson’s disease. Commun Biol. 2: Article number: 424 (2019) 15. Ikeda A, Nishioka K, Meng H, Takanashi M, Hasegawa I, Inoshita T, Shiba-Fukushima K, Li Y, Yoshino H, Mori A, Okuzumi A, Yamaguchi A, Nonaka R, Izawa N, Ishikawa KI, Saiki H, Morita M, Hasegawa M, Hasegawa K, Elahi M, Funayama M, Okano H, Akamatsu W, Imai Y, Hattori N: Mutations in CHCHD2 cause α-synuclein aggregation. Hum Mol Genet. 28(23):3895-3911 (2019) 16. Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo S-i, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N: Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling. Proc Natl Acad Sci U S A. 116: 20689–20699 (2019) 17. Wakisaka KT, Imai Y: The dawn of pirna research in various neuronal disorders. Front Biosci (Landmark Ed). 24:1440-1451 (2019) 18. Imai Y, Meng H, Shiba-Fukushima K, Hattori N: Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. Int. J. Mol. Sci. 20: 908, doi: 10.3390/ijms20040908 (2019) 19. Sugo M, Kimura H, Arasaki K, Amemiya T, Hirota N, Dohmae N, Imai Y, Inoshita T, Shiba-Fukushima K, Hattori N, Fujimoto T, Wakana Y, Inoue H, Tagaya M: Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy. EMBO J. 37, e98899 (2018) 20. Inoshita T, Cui C, Hattori N, Imai Y: Regulation of membrane dynamics by Parkinson's disease-associated genes. J Genet. 97:715-727 (2018) 21. Hosaka Y, Inoshita T, Shiba-Fukushima K, Cui C, Arano T, Imai Y, Hattori N: Reduced TDP-43 Expression Improves Neuronal Activities in a Drosophila Model of Perry Syndrome. EBioMedicine. 21: 218-227 (2017) 22. Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Hatta T, Natsume T, Umitsu M, Takagi J, Imai Y, Hattori N: Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. Nat Commun. 8, 10.1038/ncomms15500 (2017) 23. Shiba-Fukushima K, Ishikawa K-I, Inoshita T, Izawa N, Takanashi M, Sato S, Onodera O, Akamatsu W, Okano H, Imai Y, Hattori N: Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease Hum Mol Genet. 26: 3172-3185 (2017) 24. Inoshita T, Arano T, Hosaka Y, Meng H, Umezaki Y, Kosugi S, Morimoto T, Koike M, Chang H-Y, Imai Y, Hattori N: Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila. Hum Mol Genet. 6: 2933-2948 (2017) 25. Klionsky DJ, et al.: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2(1): 1-222 (2016) 26. Iyer J, Wang Q, Le T, Pizzo L, Grönke S, Ambegaokar S, Imai Y, Srivastava A, Lu B, Mardon G, Artero R, Jackson GR, Isaacs AM, Partridge L, Kumar JP, Girirajan S.: Quantitative assessment of eye phenotypes for functional genetic studies using Drosophila melanogaster. G3 6(5):1427-1437 (2016) 27. Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang C-L, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, and Takahashi R: The Parkinson’s disease-associated protein kinase LRRK2 modulates Notch signaling through the endosomal pathway. PLoS Genet. 11(9): e1005503 (2015) 28. Vaikath NN, Majbour NK, Paleologou KE, Ardah MT, van Dam E, van de Berg WD, Forrest SL, Parkkinen L, Gai WP, Hattori N, Takanashi M, Lee SJ, Mann DM, Imai Y, Halliday GM, Li JY, El-Agnaf OM: Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology. Neurobiol Dis. 30(79) 81-99 (2015) 29. Shiba-Fukushima K, Arano, T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu K-K, Nukina N, Hattori N, Imai Y: Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering. PLoS Genet. 10: e1004861 (2014) 30. Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y: Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy. J Biol. Chem. 289: 33131-33136 (2014) 31. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N: PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. PLoS Genet 10(6): e1004391 (2014)

研究テーマ

遺伝性パーキンソン病の病理メカニズムの解明

研究業績（論文）

1. Inoshita T, Liu J-Y, Taniguchi D, Ishii R, Shiba-Fukushima K, Hattori N, Imai Y: Parkinson’s disease-associated Leucine-rich repeat kinase regulates UNC-104-dependent axonal transport of Arl8-positive vesicles in Drosophila. iScience 25, 105476 (2022)

2. Tezuka T, Taniguchi D, Sano M, Shimada T, Oji Y, Tsunemi T, Ikeda A, Li Y, Yoshino H, Ogata J, Shiba-Fukushima K Funayama M, Nishioka K, Imai Y†, Hattori N†: Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson’s disease. NPJ Parkinsons Dis. 8, Article number: 97 (2022)

3. Daida K, Shimonaka S, Shiba-Fukushima K, Ogata J, Yoshino H, Okuzumi A, Hatano T, Motoi Y, Hirunagi T, Katsuno M, Shindou H, Funayama M, Nishioka K, Hattori N, Imai Y: α-Synuclein V15A variant in familial Parkinson's disease exhibits a weaker lipid-binding property. Mov Disord. 37, 2075-2085 (2022)

4. Liu J-Y, Inoshita T, Shiba-Fukushima K, Yoshida S, Ogata K, Ishihama Y, Imai Y†, Hattori N†: Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation. Hum Mol Genet. 31:2623-2638 (2022)

5. Liu J-Y, Inoshita T, Shiba-Fukushima K, Yoshida S, Ogata K, Ishihama Y, Imai Y, Hattori N: Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation. Hum Mol Genet. (2022) in press

6. Kato S, Arasaki K, Tokutomi N, Imai Y, Inoshita T, Hattori N, Sasaki T, Sato M, Wakana Y, Inoue H, Tagaya M: Syntaxin 17, an ancient SNARE paralog, plays different and conserved roles in different organisms. J Cell Sci. 134: jcs258699 (2021)

7. Hung YC, Huang KL, Chen PL, Li JL, Lu SH, Chang JC, Lin HY, Lo WC, Huang SY, Lee TT, Lin TY, Imai Y, Hattori N, Liu CS, Tsai SY, Chen CH, Lin CH, Chan CC: UQCRC1 engages cytochrome c for neuronal apoptotic cell death. Cell Rep. 36: 109729 (2021)

8. Elahi M, Motoi Y, Shimonaka S, Ishida Y, Hioki H, Takanashi M, Ishiguro K, Imai Y, Hattori N: High-fat diet-induced activation of SGK1 promotes Alzheimer's disease-associated tau pathology. Hum Mol Genet. 30: 1693-1710 (2021)

9. Ogata J, Hirao K, Nishioka K, Hayashida A, Li Y, Yoshino H, Shimizu S, Hattori N, Imai Y: A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels. Int. J. Mol. Sci. 22: 3708 (2021)

10. Kano M, Takanashi M, Oyama G, Yoritaka A, Hatano T, Shiba-Fukushima K, Nagai M, Nishiyama K, Hasegawa K, Inoshita T, Ishikawa K-i, Akamatsu W, Imai Y, Bolognin S, Schwamborn JC, Hattori N: Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations. NPJ Parkinsons Dis 6: Article number 33 (2020)

11. Masuzugawa S, Nishioka K, Imai Y, Ogata J, Shojima Y, Li Y, Yoshino H, Hattori N: A novel rare variant of LRRK2 associated with familial Parkinson's disease: p.R1501W. Parkinsonism Relat Disord 76:46-48 (2020)

12. Yamaguchi A, Ishikawa K-I, Inoshita T, Shiba-Fukushima K, Saiki S, Hatano T, Mori A, Oji Y, Okuzumi A, Li Y, Funayama M, Imai Y, Hattori N, Akamatsu W: Identifying therapeutic agents for amelioration of mitochondrial clearance disorder in neurons of familial Parkinson's disease. Stem Cell Reports. 14: 1060-1075 (2020)

13. Shiba-Fukushima K, Inoshita T, Sano O, Iwata H, Ishikawa K-i, Okano H, Akamatsu W, Imai Y, Hattori N: A cell-based high-throughput screening identified two compounds that enhance PINK1-Parkin signaling. iScience. Article number: 101048 (2020)

14. Imai Y, Inoshita T, Meng H, Shiba-Fukushima K, Hara KY, Sawamura N, Hattori N: Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson’s disease. Commun Biol. 2: Article number: 424 (2019)

15. Ikeda A, Nishioka K, Meng H, Takanashi M, Hasegawa I, Inoshita T, Shiba-Fukushima K, Li Y, Yoshino H, Mori A, Okuzumi A, Yamaguchi A, Nonaka R, Izawa N, Ishikawa KI, Saiki H, Morita M, Hasegawa M, Hasegawa K, Elahi M, Funayama M, Okano H, Akamatsu W, Imai Y, Hattori N: Mutations in CHCHD2 cause α-synuclein aggregation. Hum Mol Genet. 28(23):3895-3911 (2019)

16. Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo S-i, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N: Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling. Proc Natl Acad Sci U S A. 116: 20689–20699 (2019)

17. Wakisaka KT, Imai Y: The dawn of pirna research in various neuronal disorders. Front Biosci (Landmark Ed). 24:1440-1451 (2019)

18. Imai Y, Meng H, Shiba-Fukushima K, Hattori N: Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. Int. J. Mol. Sci. 20: 908, doi: 10.3390/ijms20040908 (2019)

19. Sugo M, Kimura H, Arasaki K, Amemiya T, Hirota N, Dohmae N, Imai Y, Inoshita T, Shiba-Fukushima K, Hattori N, Fujimoto T, Wakana Y, Inoue H, Tagaya M: Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy. EMBO J. 37, e98899 (2018)

20. Inoshita T, Cui C, Hattori N, Imai Y: Regulation of membrane dynamics by Parkinson's disease-associated genes. J Genet. 97:715-727 (2018)

21. Hosaka Y, Inoshita T, Shiba-Fukushima K, Cui C, Arano T, Imai Y, Hattori N: Reduced TDP-43 Expression Improves Neuronal Activities in a Drosophila Model of Perry Syndrome. EBioMedicine. 21: 218-227 (2017)

22. Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Hatta T, Natsume T, Umitsu M, Takagi J, Imai Y, Hattori N: Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. Nat Commun. 8, 10.1038/ncomms15500 (2017)

23. Shiba-Fukushima K, Ishikawa K-I, Inoshita T, Izawa N, Takanashi M, Sato S, Onodera O, Akamatsu W, Okano H, Imai Y, Hattori N: Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease Hum Mol Genet. 26: 3172-3185 (2017)

24. Inoshita T, Arano T, Hosaka Y, Meng H, Umezaki Y, Kosugi S, Morimoto T, Koike M, Chang H-Y, Imai Y, Hattori N: Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila. Hum Mol Genet. 6: 2933-2948 (2017)

25. Klionsky DJ, et al.: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2(1): 1-222 (2016)

26. Iyer J, Wang Q, Le T, Pizzo L, Grönke S, Ambegaokar S, Imai Y, Srivastava A, Lu B, Mardon G, Artero R, Jackson GR, Isaacs AM, Partridge L, Kumar JP, Girirajan S.: Quantitative assessment of eye phenotypes for functional genetic studies using Drosophila melanogaster. G3 6(5):1427-1437 (2016)

27. Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang C-L, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, and Takahashi R: The Parkinson’s disease-associated protein kinase LRRK2 modulates Notch signaling through the endosomal pathway. PLoS Genet. 11(9): e1005503 (2015)

28. Vaikath NN, Majbour NK, Paleologou KE, Ardah MT, van Dam E, van de Berg WD, Forrest SL, Parkkinen L, Gai WP, Hattori N, Takanashi M, Lee SJ, Mann DM, Imai Y, Halliday GM, Li JY, El-Agnaf OM: Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology. Neurobiol Dis. 30(79) 81-99 (2015)

29. Shiba-Fukushima K, Arano, T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu K-K, Nukina N, Hattori N, Imai Y: Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering. PLoS Genet. 10: e1004861 (2014)

30. Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y: Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy. J Biol. Chem. 289: 33131-33136 (2014)

31. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N: PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. PLoS Genet 10(6): e1004391 (2014)

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研究業績詳細

今居 譲（イマイ ユズル）

今居譲（イマイユズル）