A pathogenesis study of Perry syndrome

• Project/Area Number: 26860678
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Fukuoka University
• Principal Investigator: Mishima Takayasu 福岡大学, 医学部, 助教 (00600602)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Perry症候群 / DCTN1 / TDP-43 / モデルマウス / iPS細胞 / 診断基準 / トランスジェニックマウス / ダイナクチン / 家族性パーキンソン病 / パーキンソン病

Outline of Final Research Achievements

【Clinical study】We reported clinical features of patients with Perry syndrome. We established international diagnostic criteria for Perry syndrome.
【Basic study】We showed that Perry syndrome is a distinctive type of TDP-43 proteinopathy. We generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient and differentiated iPSCs into tyrosine hydroxylase (TH)-positive neurons. TH-positive neurons from a patient with Perry syndrome had dynactin aggregations in cytoplasm. Patient TH-positive neurons recapitulated an aspect of the disease phenotype of Perry syndrome. We generated DCTN1 G71A transgenic mice. These mice showed decreased exploratory activity and impaired motor coordination. These behavioral defects paralleled apathy-like symptoms and parkinsonism encountered in Perry syndrome.

Research Products

• [Int'l Joint Research] Department of Neuroscience, Mayo Clinic/Department of Neurology, Mayo Clinic(米国)
• [Int'l Joint Research] University of British Columbia(カナダ)
• [Int'l Joint Research]
• [Int'l Joint Research] Mayo Clinic Jacksonville(米国)
• [Journal Article] Establishing diagnostic criteria for Perry syndrome (2018)
  • Author(s): Mishima T, Fujioka S, Tomiyama H, Yabe I, Kurisaki R, Fujii N, Neshige R, Ross OA, Farrer MJ, Dickson DW, Wszolek ZK, Hattori N, Tsuboi Y
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 89 Issue: 5 Pages: 482-487
  • DOI: 10.1136/jnnp-2017-316864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Behavioral defects in a DCTN1 G71A transgenic mouse model of Perry syndrome (2018)
  • Author(s): Mishima T, Deshimaru M, Watanabe T, Kubota K, Kinoshita-Kawada M, Yuasa-Kawada J, Takasaki K, Uehara Y, Jinno S, Iwasaki K, Tsuboi Y
  • Journal Title: Neurosci Lett Volume: 666 Pages: 98-103
  • Peer Reviewed
• [Journal Article] Perry症候群 (2018)
  • Author(s): 三嶋崇靖，坪井義夫
  • Journal Title: Frontiers in Parkinson Disease Volume: 11 Pages: 28-31
• [Journal Article] Dysphagia in Perry syndrome: pharyngeal pressure of two cases (2017)
  • Author(s): Umemoto G, Tsuboi Y, Furuya H, Mishima T, Fujioka S, Fujii N, Arahata H, Sugahara M, Sakai M
  • Journal Title: Case report in Neurology Volume: 9 Issue: 2 Pages: 161-167
  • DOI: 10.1159/000457900
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reduced orexin immunoreactivity in Perry syndrome and multiple system atrophy (2017)
  • Author(s): Mishima T, Kasanuki K, Koga S, Castanedes-Casey M, Wszolek ZK, Tsuboi Y, Dickson DW
  • Journal Title: Parkinsonism Relat Disord Volume: 42 Pages: 85-89
  • DOI: 10.1016/j.parkreldis.2017.06.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Perry Syndrome: A Distinctive type of TDP-43 Proteinopathy (2017)
  • Author(s): Mishima T, Koga S, Lin WL, Kasanuki K, Castanedes-Casey M, Wszolek ZK, Oh SJ, Tsuboi Y, Dickson DW
  • Journal Title: J Neuropathol Exp Neurol Volume: 76 Issue: 8 Pages: 676-682
  • DOI: 10.1093/jnen/nlx049
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome (2016)
  • Author(s): Mishima T, Ishikawa T, Imamura K, Kondo T, Koshiba Y, Takahashi R, Takahashi J, Watanabe A, Fujii N, Tsuboi Y, Inoue H
  • Journal Title: Parkinsonism & Related Disorders Volume: 30 Pages: 67-72
  • DOI: 10.1016/j.parkreldis.2016.06.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impulse control disorders and punding in Perry syndrome. (2015)
  • Author(s): Mishima T, Fujioka S, Kurisaki R, Yanamoto S, Higuchi MA, Tsugawa J, Fukae J, Neshige R, Tsuboi Y
  • Journal Title: Parkinsonism & Related Disorders Volume: ２１ Issue: 11 Pages: 1381-1382
  • DOI: 10.1016/j.parkreldis.2015.09.037
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Perry syndrome is a distinctive type of TDP-43 proteinopathy (2017)
  • Author(s): Mishima T, Koga S, Lin WL, Kasanuki K, Castanedes-Casey M, Wszolek ZK, Oh SJ, Tsuboi Y, Dickson DW
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Human iPSC disease modeling of Perry syndrome (2017)
  • Author(s): Mishima T, Ishikawa T, Imamura K, Kondo T, Koshiba Y, Takahashi R, Takahashi J, Watanabe A, Fujii N, Tsuboi Y, Inoue H
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Disease modeling for Perry syndrome using patient induced pluripotent stem cells (2017)
  • Author(s): Mishima T, Ishikawa T, Imamura K, Kondo T, Koshiba Y, Takahashi R, Takahashi J, Watanabe A, Fujii N, Tsuboi Y, Inoue H
  • Organizer: 21th International Congress of Parkinson's Disease and Movement Disorders
  • Int'l Joint Research
• [Presentation] Perry症候群におけるマイネルト基底核のオレキシン染色性の低下 (2017)
  • Author(s): 三嶋 崇靖, 笠貫 浩史, 古賀 俊輔, Monica Castanedes-Casey, Zbigniew K. Wszolek, 坪井 義夫, Dennis W. Dickson
  • Organizer: 第11回パーキンソン病運動障害疾患コングレス
• [Presentation] A cellular model for Perry syndrome using patient iPSCs (2016)
  • Author(s): Mishima T, Ishikawa T, Imamura K, Kondo T, Koshiba Y, Takahashi R, Takahashi J, Watanabe A, Fujii N, Tsuboi Y, Inoue H
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター(兵庫・神戸市)
  • Year and Date: 2016-05-18
• [Presentation] Impulse control disorders and punding in Perry syndrome (2015)
  • Author(s): Mishima T, Fujioka S, Kurisaki R, Yanamoto S, Higuchi MA, Tsugawa J, Fukae J, Neshige R, Tsuboi Y
  • Organizer: XXI Word Congress on Parkinson’s disease and Related Disorders
  • Place of Presentation: イタリア
  • Year and Date: 2015-12-06
  • Int'l Joint Research