The effects of phosphorylation on degradative processes of abnormally accumulated intracellular protein in dementia

• Project/Area Number: 15K09828
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: Tanaka Toshihisa 大阪大学, 医学系研究科, 准教授 (10294068)
• Co-Investigator(Kenkyū-buntansha): 森原 剛史 大阪大学, 医学系研究科, 助教 (90403196)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: タウ蛋白 / TDP-43 / リン酸化 / 認知症

Outline of Final Research Achievements

Degradative processes of abnormally accumulated intracellular protein in dementia, are still unknown. We studied effects of phosphorylation of the protein on the degradative processes. Ubiquitination and its priming proteolysis of tau was not affected by phosphorylation. Proteolysis of TDP-43 by caspase was not affected by phosphorylation. However incorporation of tau into lysosome in chaperone-mediated autophagy was increased by PKA-phosphorylation. It is suggested that some of degradative processes of tau might be affected by its phosphorylation.

Research Products

• [Journal Article] Usefulness of carer-held records to support informal caregivers of patients with dementia who live at home. (2018)
  • Author(s): Sato S, Kazui H, Shimizu Y, Yoshida T, Yoshiyama K, Kanemoto H, Suzuki Y, Morikami T, Fujisue H, Tanaka T, Ikeda M.
  • Journal Title: Psychogeriatrics. 2018 Feb 6. Volume: 16 Issue: 3 Pages: 154-164
  • DOI: 10.1111/psyg.12304
  • Peer Reviewed
• [Journal Article] 現在考えられているアルツハイマー型認知症のメカニズムと薬物療法の可能性 (2018)
  • Author(s): 田中稔久
  • Journal Title: 臨床精神薬理 Volume: 21 Pages: 3-18
  • NAID: 40021453645
• [Journal Article] Effects of donepezil on sleep disturbances in patients with dementia with Lewy bodies An open-label study with actigraphy. (2017)
  • Author(s): Kazui H, Adachi H, Kanemoto H, Yoshiyama K, Wada T, Tokumasu Nomura K, Tanaka T, Ikeda M
  • Journal Title: Psychiatry Res Volume: 251 Pages: 312-318
  • DOI: 10.1016/j.psychres.2017.02.039
  • Peer Reviewed
• [Journal Article] Neural Basis of Apathy in Patients with Amnestic Mild Cognitive Impairment (2017)
  • Author(s): Kazui H, Takahashi R, Yamamoto Y, Yoshiyama K, Kanemoto H, Suzuki Y, Sato S, Azuma S, Suehiro T, Shimosegawa E, Ishii K, Tanaka T.
  • Journal Title: J Alzheimers Dis. Volume: 55(4) Issue: 4 Pages: 1403-1416
  • DOI: 10.3233/jad-160223
  • Peer Reviewed
• [Journal Article] アミロイド蓄積とタウタンパク、タウオパチーに関する最近の知見 (2017)
  • Author(s): 田中稔久
  • Journal Title: 老年精神医学雑誌 Volume: 28 Pages: 115-122
• [Journal Article] 字形想起障害による漢字の純粋失書を認め、皮質基底核症候群を呈したアルツハイマー病の1例 (2017)
  • Author(s): 鐘本英輝、数井裕光、鈴木由希子、佐藤俊介、吉山顕次、田中稔久
  • Journal Title: 高次脳機能研究 Volume: 37 Pages: 15-21
  • NAID: 130006602681
  • Peer Reviewed
• [Journal Article] リスク因子を背負った認知症治療研究 (2017)
  • Author(s): 田中稔久 池田学
  • Journal Title: Brain and Nerve Volume: 69 Pages: 15-21
• [Journal Article] Sleep disturbances are key symptoms of very early stage Alzheimer disease with behavioral and psychological symptoms: a Japan multi-center cross-sectional study (J-BIRD). (2016)
  • Author(s): Kabeshita Y, Adachi H, Matsushita M, Kanemoto H, Sato S, Suzuki Y, Yoshiyama K, Shimomura T, Yoshida T, Shimizu H, Matsumoto T, Mori T, Kashibayashi T, Tanaka H, Hatada Y, Hashimoto M, Nishio Y, Komori K, Tanaka T, Yokoyama K, Tanimukai S, Ikeda M, Takeda M, Mori E, Kudo T, Kazui H.
  • Journal Title: Int J Geriatr Psychiatry. Volume: - Issue: 2 Pages: 222-230
  • DOI: 10.1002/gps.4470
  • Peer Reviewed
• [Journal Article] Functional connectivity assessed by resting state EEG correlates with cognitive decline of Alzheimer's disease - An eLORETA study. (2016)
  • Author(s): Hata M, Kazui H, Tanaka T, Ishii R, Canuet L, Pascual-Marqui RD, Aoki Y, Ikeda S, Kanemoto H, Yoshiyama K, Iwase M, Takeda M.
  • Journal Title: Clin Neurophysiol. Volume: 127(2) Issue: 2 Pages: 1269-78
  • DOI: 10.1016/j.clinph.2015.10.030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ssociation between high biomarker probability of Alzheimer's disease and improvement of clinical outcomes after shunt surgery in patients with idiopathic normal pressure hydrocephalus. (2016)
  • Author(s): Kazui H, Kanemoto H, Yoshiyama K, Kishima H, Suzuki Y, Sato S, Suehiro T, Azuma S1), Yoshimine T, Tanaka T
  • Journal Title: J Neurol Sci. Volume: 369 Pages: 236-241
  • DOI: 10.1016/j.jns.2016.08.040
  • Peer Reviewed
• [Journal Article] Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias (2016)
  • Author(s): Kazui H, Yoshiyama K, Kanemoto H, Suzuki Y, Sato S, Hashimoto M, Ikeda M, Tanaka H, Hatada Y, Matsushita M, Nishio Y, Mori E, Tanimukai S, Komori K, Yoshida T, Shimizu H, Matsumoto T, Mori T, Kashibayashi T, Yokoyama K, Shimomura T, Kabeshita Y, Adachi H, Tanaka T
  • Journal Title: PLoS One Volume: 11 Issue: 8 Pages: e0161092-e0161092
  • DOI: 10.1371/journal.pone.0161092
  • Peer Reviewed / Open Access
• [Journal Article] 認知機能低下に対する薬物療法―根治的治療薬開発の現状 (2016)
  • Author(s): 田中稔久
  • Journal Title: 臨床精神薬理 Volume: 19 Pages: 101-108
  • Peer Reviewed
• [Journal Article] Association of CSF tap-related oscillatory activity and shunt outcome in idiopathic normal pressure hydrocephalus. (2015)
  • Author(s): Ikeda S, Kazui H, Tanaka T, Ishii R, Aoki Y, Hata M, Canuet L, Yoshiyama K, Iwase M, Takeda M.
  • Journal Title: Psychogeriatrics. Volume: 15 Pages: 191-197
  • Peer Reviewed
• [Journal Article] Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus. (2015)
  • Author(s): Aoki Y, Kazui H, Tanaka T, Ishii R, Wada T, Ikeda S, Hata M, Canuet L, Katsimichas T, Musha T, Matsuzaki H, Imajo K, Kanemoto H, Yoshida T, Nomura K, Yoshiyama K, Iwase M, Takeda M
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 1-5
  • DOI: 10.1038/srep07775
  • Peer Reviewed / Open Access
• [Journal Article] Resting-state synchrony between the retrosplenial cortex and anterior medial cortical structures relates to memory complaints in subjective cognitive impairment. (2015)
  • Author(s): Yasuno F, Kazui H, Yamamoto A, Morita N, Kajimoto K, Ihara M, Taguchi A, Matsuoka K, Kosaka J, Tanaka T, Kudo T, Takeda M, Nagatsuka K, Iida H, Kishimoto T.
  • Journal Title: Neurobiol Aging. Volume: 36 Pages: 2145-2152
  • Peer Reviewed
• [Presentation] タウの分子病理と治療薬開発 (2016)
  • Author(s): 田中稔久
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
  • Invited
• [Presentation] 抗認知症薬の薬理作用とその期待される効果 (2015)
  • Author(s): 田中稔久
  • Organizer: 第20回認知神経科学会学術集会
  • Place of Presentation: 東京大学
  • Year and Date: 2015-08-09
  • Invited
• [Presentation] 認知症性疾患の分子病態 -タウ蛋白を中心に- (2015)
  • Author(s): 田中稔久
  • Organizer: 第15回奈良認知症研究会
  • Place of Presentation: 奈良
  • Year and Date: 2015-07-30
  • Invited
• [Presentation] CSF biomarkers in differential diagnosis of dementia. (2015)
  • Author(s): Tanaka T, terada M, Sato M, Takeda M.
  • Organizer: The 12th World Congress of Biological Psychiatry (WFSBP2015).
  • Place of Presentation: Athen, Greece
  • Year and Date: 2015-06-14
  • Int'l Joint Research