Juntendo University, Tokyo, established in 1838.

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Department of Research for Parkinson's Disease

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Publication

 Original articles (2000-2024)

  1. Ikeda A, Meng H, Taniguchi D, Mio M, Funayama M, Nishioka K, Yoshida M, Li Y, Yoshino H, Inoshita T, Shiba-Fukushima K, Okubo Y, Sakurai T, Amo T, Aiba I, Saito Y, Saito Y, Murayama S, Atsuta N, Nakamura R, Tohnai G, Izumi Y, Morita M, Tamura A, Kano O, Oda M, Kuwabara S, Yamashita T, Sone J, Kaji R, Sobue G, Imai Y, Hattori N: CHCHD2 P14L, found in amyotrophic lateral sclerosis, exhibits cytoplasmic mislocalization and alters Ca2+ homeostasis. PNAS Nexus 3, pgae319 (2024)
  2. Tezuka T, Ishiguro M, Taniguchi D, Osogaguchi E, Shiba-Fukushima K, Ogata J, Ishii R, Ikeda A, Li Y, Yoshino H, Matsui T, Kaida K, Funayama M, Nishioka K, Kumazawa F, Matsubara T, Tsuda H, Saito Y, Murayama S, Imai Y, Hattori N: Clinical characteristics and pathophysiological properties of newly discovered LRRK2 variants associated with Parkinson’s disease. Neurobiol Dis. 199: 106571 (2024)
  3. 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)
  4. 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)
  5. 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. (2022) in press
  6. 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)
  7. 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)
  8. 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)
  9. 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. 18: 1693–1710 (2021)
  10. 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)
  11. 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)
  12. 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)
  13. 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)
  14. 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: 424 (2020)
  15. 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)
  16. 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. 28:3895-3911 (2019) 
  17. 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)
  18. 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)
  19. Inoshita T, Hattori N, Imai Y: Live Imaging of Axonal Transport in the Motor Neurons of Drosophila Larvae Bio-Protocol 7 (23): e2631 (2017)
  20. 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)
  21. 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)
  22. 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)
  23. 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. 26: 2933-2948 (2017)
  24. Iyer J, Wang Q, Le T, Pizzo L, Gronke S, Ambegaokar S, Imai Y, Srivastava A, Llamusi Troisi 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)
  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. 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)
  27. 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. 79: 81-99 (2015)
  28. 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 (2014b) This article is featured in a mini review: A Polyubiquitin Chain Reaction: Parkin Recruitment to Damaged Mitochondria.PLoS Genet.11: e1004952 (2015)
  29. 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)
  30. Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y: PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. PLoS Genet.10(6): e1004391 (2014a)
  31. Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B: Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance. Genes Dev. 27:157-162 (2013)
  32. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N: PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep. 2: Article number: 1002 (2012)
  33. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton WM, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B: Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 8: e1002537 (2012)
  34. Kanao T, Sawada T, Davies S-A, Ichinose H, Hasegawa K, Takahashi R, Hattori N, Imai Y: The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila. PLoS ONE. 7: e30958 (2012)
  35. Imai Y, Lu B: Mitochondrial Dynamics and Mitophagy in Parkinson's disease: Disordered cellular power plant becomes a big deal in a major movement disorder. Curr Opin Neurobiol. 21: 935–941 (2011)
  36. Imai Y, Kanao T, Sawada T, Kobayashi Y, Moriwaki Y, Ishida Y, Takeda K, Ichijo H, Lu B, Takahashi R: The Loss of PGAM5 Suppresses the Mitochondrial Degeneration Caused by Inactivation of PINK1 in Drosophila. PLoS Genet. 6: e1001229 (2010)
  37. Kanao T, Venderova K, Park DS, Unterman T, Lu B, Imai Y: Activation of FoxO by LRRK2 induces expression of proapoptotic proteins and alters survival of postmitotic dopaminergic neuron in Drosophila. Hum Mol Genet. 19: 3747-3758 (2010)
  38. Gehrke S, Imai Y, Sokol N, Lu B: Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 466: 637-641 (2010)
  39. Imai Y, Gehrke S, Wang HQ, Takahashi R, Hasegawa K, Oota E, Lu B: Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J. 27: 2432-2443 (2008)
  40. Wang HQ, Imai Y, Inoue H, Kataoka A, Iita S, Takahashi R: Pael-R transgenic mice crossed with parkin deficient mice displayed progressive and selective catecholaminergic neuronal loss. J Neurochem. 107: 171-185 (2008)
  41. Wang J-W, Imai Y, Lu B: Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1. J Neurosci.  27: 2457-2467 (2007)
  42. Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, Namekawa K, Kiyama H, Stern DM, Hori O, Wakamatsu K, Ito S, Itohara S, Takahashi R, Ogawa S: Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of Parkin inactivation. Hum Mol Genet.16: 50-60 (2007)
  43. Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang J-W, Yang L, Beal MF, Vogel H, Lu B: Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by Drosophila PINK1 is rescued by Parkin. Proc Natl Acad Sci U S A. 103: 10793-10798 (2006)
  44. Yang Y, Gehrke S, Haque ME, Imai Y, Kosek J, Yang L, Beal MF, Nishimura I, Wakamatsu K, Ito S, Takahashi R, Lu B: Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci U S A. 102: 13670-13675 (2005)
  45. Imai Y and Takahashi R: How do Parkin mutations result in neurodegeneration? Curr Opin Neurobiol. 14: 384-389 (2004)
  46. Yang Y, Nishimura I, Imai Y, Takahashi R, Lu B: Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron. 37: 911-924 (2003)
  47. Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K-I, Takahashi R: CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell. 10: 55-67 (2002)
  48. Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R: A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell. 8: 613-621 (2001)
  49. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R: An unfolded putative membrane transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell. 105: 891-902 (2001)
  50. Imai Y, Soda M, Takahashi R: Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem. 275: 35661-35664 (2000)

 Review articles (2003-2023)

  1. Iseki T, Imai Y, Hattori N: Is glial dysfunction the key pathogenesis of LRRK2-linked Parkinson's disease? Biomolecules 13, 178 (2023)
  2. Ikeda A, Imai Y, Hattori N: Neurodegeneration-associated mitochondrial proteins, CHCHD2 and CHCHD10–what distinguishes the two? Front. Cell. Dev. Biol. doi: 10.3389/fcell.2022.996061 (2022)
  3. Nishioka K, Imai Y, Yoshino H, Li Y, Funayama M, Hattori N: Clinical Manifestations and Molecular Backgrounds of Parkinson’s Disease Regarding Genes Identified from Familial and Population Studies. Front. Neurol. doi: 10.3389/fneur.2022.764917 (2022)
  4. Experimental Models of Parkinson’s Disease. Methods Mol Biol., Imai Y ed., Springer, 2322: 207-214 (2021)
  5. Imai Y, Kim K, Wu Z, Sato S：Editorial: Molecular Links Between Mitochondrial Damage and Parkinson'sDisease and Related Disorders. Front Cell Dev Biol. 9: 734475 (2021)
  6. Imai Y: Editorial for the Special Issue “Animal Models of Parkinson’s Disease and Related Disorders”. Int. J. Mol. Sci. 21: 4250 (2020)
  7. Mori A, Imai Y, Hattori N: Lipids: Key players that modulate α-synuclein toxicity and neurodegeneration in Parkinson’s disease. Int. J. Mol. Sci. 21: 3301 (2020)
  8. Imai Y: PINK1-Parkin signaling in Parkinson's disease: Lessons from Drosophila. Neurosci Res. S0168-0102(20)30066-3 (2020)
  9. Wakisaka KT, Imai Y: The dawn of pirna research in various neuronal disorders. Front Biosci (Landmark Ed). 24:1440-1451 (2019).
  10. 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)
  11. Inoshita T, Cui C, Hattori N, Imai Y: Regulation of membrane dynamics by Parkinson's disease-associated genes. J Genet. 97:715-727 (2018)
  12. Hattori N, Arano T, Hatano T, Mori A, Imai Y: Mitochondrial-Associated Membranes in Parkinson's Disease. Adv Exp Med Biol. 997:157-169 (2017)
  13. Meng H, Yamashita C, Hattori N, Imai Y: Measurements of the mitochondrial respiration and glycolytic activity in Drosophila embryonic cells. Protocol Exchange doi:10.1038/protex.2017.069 (2017)
  14. Inoshita T, Shiba-Fukushima K, Meng H, Hattori N, Imai Y: Monitoring Mitochondrial Changes by Alteration of the PINK1-Parkin Signaling inDrosophila. Methods Mol Biol. doi: 10.1007/7651_2017_9 (2017)
  15. Inoshita T, Imai Y: Disturbances in Mitochondrial Function and Vesicular Transport as Mechanisms for Pathogenesis in Parkinson's Disease. In: Horizons in Neuroscience Research Vol. 29, Costa A and Villalba E ed, Nova Biomedical, New York, Chapter 2, 89-115.
  16. Inoshita T, Imai Y: Regulation of vesicular trafficking by Parkinson's disease-associated genes. AIMS Mol Sci,  2(4): 461-475 (2015)
  17. Arano T, Imai Y: Mitophagy regulated by the PINK1-Parkin pathway. In: Cell Death - Autophagy, Necrosis and Apoptosis, Simcic I ed, InTech, Rijeka, Chapter 6, 113-131.
  18. Inoshita T, Imai Y: Ubiquitin ligase-assisted selective autophagy of mitochondria: Determining its biological significance using Drosophila models. In: Autophagy Vol. 4: Cancer, Other Pathologies, Inflammation, Immunity, and Infection, Hayat MA ed, Elsevier, Amsterdam, Chapter 9, 151-162.
  19. Imai Y, Hattori N: Mitophagy Controlled by the PINK1-Parkin Pathway is Associated with Parkinson's Disease Pathogenesis. In: Autophagy Vol. 4: Cancer, Other Pathologies, Inflammation, Immunity, and Infection, Hayat MA ed, Elsevier, Amsterdam, Chapter 15, 227-238.
  20. Hattori N, Saiki S, Imai Y: Regulation by mitophagy. Int J Biochem Cell Biol. 53 : 147–150 (2014)
  21. Lee S, Imai Y, Gehrke S, Liu S, Lu B: The synaptic function of LRRK2. Biochem Soc Trans. 40:1047-1051 (2012)
  22. Imai Y: Mitochondrial regulation by the PINK1-Parkin signaling. ISRN Cell Biol. 2012: Article ID 926160 (2012)
  23. Imai Y, Venderova K, Lim K-L: Editorial; Animal models of Parkinson's disease. Parkinsons Dis. 2012: Article ID 729428 (2012)
  24. Imai Y, Lu B: Mitochondrial Dynamics and Mitophagy in Parkinson's disease: Disordered cellular power plant becomes a big deal in a major movement disorder. Curr Opin Neurobiol. 21: 935–941 (2011)
  25. Imai Y, Venderova K, Park DS, Cai H, Schmidt E: Editorial; Animal models of Parkinson's disease. Parkinsons Dis. 2011: Article ID 364328 (2011)
  26. Imai Y: Dysregulation of microRNA-mediated translational repression is involved in neurodegeneration in a Drosophila model of Parkinson's disease. Bulletin 75: 39-56 (2011)
  27. Imai Y and Takahashi R: Parkinson's disease and ER stress. In: Molecular mechanisms in Parkinson's disease. Kähle P and Haass C eds, Georgetown: Landes Biosci. (2005)
  28. Imai Y and Takahashi R: How do Parkin mutations result in neurodegeneration? Curr Opin Neurobiol. 14: 384-389 (2004)
  29. Takahashi R and Imai Y: Pael receptor, endoplasmic reticulum stress, and Parkinson's disease. J Neurol. 250 Suppl 3: III25-29 (2003)
  30. Takahashi R, Imai Y, Hattori N, Mizuno Y: Parkin and endoplasmic reticulum stress. Ann N Y Acad Sci. 991: 101-106 (2003)
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