Effects of A2A-receptor antagonists on PD models via autophagy regulation.

• Project/Area Number: 23689046
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: SAIKI Shinji 順天堂大学, 医学部, 准教授 (00339996)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 脳神経疾患 / 国際情報交換 / オートファジー / パーキンソン病 / 神経変性疾患

Research Abstract

Considering caffeine preventive effects on Parkinson's disease, we examined effects of caffeine analogues on PD cellular models via autophagic regulation using cellular models.
HeLa cells treated with a caffeine analogue have shown characteristics of autophagic inhibition via mTOR independent pathway, especially via cAMP. Also, one of them induced cell death in some cell lines but not in others. Taken together, some caffeine analogues might be potential candidates for anti-cancer agents.

Research Products

• [Journal Article] p150^<glued>-associated disorders are caused by activation of intrinsic apoptotic pathway (2014)
  • Author(s): Ishikawa K, Saiki S, Furuya N, Yamada D, Imamichi Y, Li Y, Kawajiri S, Sasaki H, Koike M, Tsuboi Y, Hattori N
  • Journal Title: PLOS ONE Volume: 9
• [Journal Article] Identification of licopyranocoumarin and glycyrurol from herbal medicines as neuroprotective compounds for Parkinson's disease. (2014)
  • Author(s): Fujimaki T, Saiki S, Tashiro E, Yamada D, Kitagawa M, Hattori N, Imoto M
  • Journal Title: PLOS ONE Volume: in press
  • Peer Reviewed
• [Journal Article] p150glued-associated disorders are caused by activation of intrinsic apoptotic pathway. (2014)
  • Author(s): Ishikawa K, Saiki S, Furuya N, Yamada D, Imamichi Y, Li Y, Kawajiri S, Sasaki H, Koike M, Tsuboi Y, Hattori N
  • Journal Title: PLOS ONE Volume: in press
  • NAID: 40020259609
  • Peer Reviewed
• [Journal Article] ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons (2013)
  • Author(s): Matsui H, Sato F, Sato S, Koike M, Taruno Y, Saiki S, Funayama M, Ito H, Taniguchi Y, Uemura N, Toyoda A, Sakaki Y, Takeda S, Uchiyama Y, Hattori N, Takahashi R
  • Journal Title: F EBS Lett Volume: 587 Pages: 1316-25
• [Journal Article] ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons. (2013)
  • Author(s): Matsui H, Sato F, Sato S, Koike M, Taruno Y, Saiki S, Funayama M, Ito H, Taniguchi Y, Uemura N, Toyoda A, Sakaki Y, Takeda S, Uchiyama Y, Hattori N, Takahashi R.
  • Journal Title: FEBS Lett Volume: 587(9) Issue: 9 Pages: 1316-1325
  • DOI: 10.1016/j.febslet.2013.02.046
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathogenesis of Parkinson disease : update (2012)
  • Author(s): Saiki S, Sato S, Hattori N
  • Journal Title: J Neurol Neurosurg Psychiat Volume: 83 Pages: 430-6
• [Journal Article] Mutations in the novel protein PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions (2012)
  • Author(s): Lee HY, Huang Y, Bruneau N, Roll P, Roberson EDO, Hermann M, Quinn E, Maas J, Edwards R, Ashizawa T, Baykan B, Bhatia K, Bressman S, Bruno MK, Brunt ER, Caraballo R, Echenne B, Fejerman N, Frucht S, Gurnett CA, Hirsch E, Houlden H, Jankovic J, Lee WL, Lynch DR, Mohamed S, Müller U, Nespeca MP, Renner D, Rochette J, Rudolf G, Saiki S, Soong BW, Swoboda KJ, Tucker S, Wood N, Hanna M, Bowcock A, Szepetowski P, Fu YH, Ptáček LJ
  • Journal Title: Cell Reports Volume: 1 Pages: 2-12
• [Journal Article] Molecular pathogenesis of Parkinson's disease : update (2012)
  • Author(s): Shinji Saiki, et al
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 83 Issue: 4 Pages: 430-436
  • DOI: 10.1136/jnnp-2011-301205
  • Peer Reviewed
• [Journal Article] Genetic mutations and functions of PINK1 (2011)
  • Author(s): Kawajiri S, Saiki S, Sato S, Hattori N
  • Journal Title: Trends Pharmacol Sci Volume: 32 Pages: 573-80
• [Journal Article] DJ-1 associates with synaptic membranes (2011)
  • Author(s): Usami Y, Hatano T, Imai S, Kubo S, Sato S, Saiki S, Fujioka Y, Ohba Y, Sato F, Funayama M, Eguchi H, Shiba K, Ariga H, Shen J, Hattori N
  • Journal Title: Neurobiol Dis Volume: 43 Pages: 651-62
• [Journal Article] Lysosomal positioning coordinates cellular nutrient responses (2011)
  • Author(s): Korolchuk V, Saiki S, Lichtenberg M, Siddiqi F, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, O'Kane CJ, Deretic V and Rubinsztein DC
  • Journal Title: Nat Cell Biol Volume: 13 Pages: 453-60
• [Journal Article] Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition (2011)
  • Author(s): Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Kei-Ichi Ishikawa, Sato S, Imoto M, Hattori N
  • Journal Title: Autophagy Volume: 7 Pages: 176-87
• [Journal Article] Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects (2011)
  • Author(s): Amo T, Sato S, Saiki S, Wolf AM, Toyomizu M, Gautier CA, Shen J, Ohta S, Hattori N
  • Journal Title: Neurobiol Dis Volume: 41 Pages: 111-8
• [Journal Article] Identification of licopyranocoumarin and glycyrurol from herbal medicines as neuroprotective compounds for Parkinson's disease
  • Author(s): Fujimaki T, Saiki S, Tashiro E, Yamada D, Kitagawa M, Hattori N, Imoto M
  • Journal Title: PLOS ONE Volume: (in press)
• [Presentation] パーキンソン病と慢性炎症 (2014)
  • Author(s): 斉木臣二
  • Organizer: 第55回日本神経学会総会
  • Place of Presentation: 福岡国際会議場等福岡県
• [Presentation] パーキンソン病とオートファジー (2014)
  • Author(s): 斉木臣二
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Invited
• [Presentation] パーキンソン病と慢性炎症 (2014)
  • Author(s): 斉木臣二
  • Organizer: 第55回日本神経学会総会
  • Place of Presentation: 福岡国際会議場等
  • Invited
• [Presentation] パーキンソン病の臨床と創薬-オートファジーとの関連を中心に- (2013)
  • Author(s): 斉木臣二
  • Organizer: 第33回ゲノム創薬フォーラム
  • Place of Presentation: 東京大学医科学研究所東京都
  • Year and Date: 2013-07-25
• [Presentation] パーキンソン病病態とオートファジーの関連について (2013)
  • Author(s): 斉木臣二
  • Organizer: 文部科学省科学研究費補助金新学術領域細胞内ロジスティクス・シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場兵庫県
• [Presentation] オートファジーを標的としたパーキンソン病治療について (2013)
  • Author(s): 斉木臣二
  • Organizer: 文部科学省科学研究費補助金新学術領域オートファジーの集学的研究シンポジウム・オートファジー研究会
  • Place of Presentation: ヤマハリゾート嬬恋静岡県
• [Presentation] パーキンソン病の臨床と創薬 -オートファジーとの関連を中心に- (2013)
  • Author(s): 斉木臣二
  • Organizer: 第33回ゲノム創薬フォーラム
  • Place of Presentation: 東京大学医科学研究所
  • Invited
• [Presentation] パーキンソン病病態とオートファジーの関連について (2013)
  • Author(s): 斉木臣二
  • Organizer: 文部科学省科学研究費補助金 新学術領域 細胞内ロジスティクスシンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場
  • Invited
• [Presentation] オートファジーを標的としたパーキンソン病治療について (2013)
  • Author(s): 斉木臣二
  • Organizer: 文部科学省科学研究費補助金 新学術領域 オートファジーの集学的研究シンポジウム・オートファジー研究会
  • Place of Presentation: ヤマハリゾート嬬恋
  • Invited
• [Presentation] EFFECTS OF CAFFEINE AND CAFFEINE ANALOGUES ON AUTOP HAGY IN CULTURED CELLS (2011)
  • Author(s): Shinji Saiki, 他
  • Organizer: Autophagy in health and Disease (EMBO conference)
  • Place of Presentation: Israel
  • Year and Date: 2011-10-30
• [Book] Neuroacanthocytosis. In : Jankovic J, Tolosa E, eds. Parkinson's disease and movement disorders. 6th ed. Philadelphia, PA : Lippincott Williams & Wilkins (2014)
  • Author(s): Saiki S
  • Publisher: (in press)
• [Remarks] 所属教室ホームページ(順天堂大学脳神経内科)
  • URL: http://www.juntendo-neurology.com/
• [Remarks] 研究グループ紹介ページ
  • URL: http://www.juntendo-neurology.com/pdf/kenkyu-saeki-furuya.pdf
• [Remarks] 順天堂大学脳神経内科
  • URL: http://www.juntendo-neurology.com/
• [Remarks] 化合物による治療探索研究・オートファジー関連研究
  • URL: http://www.juntendo-neurology.com/pdf/kenkyu-saeki-furuya.pdf
• [Patent(Industrial Property Rights)] パーキンソン病予防治療剤 (2013)
  • Inventor(s): 服部信孝、斉木臣二、井本正哉、藤 巻貴宏
  • Industrial Property Rights Holder: 学校法人順天堂
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-25
  • Overseas
• [Patent(Industrial Property Rights)] パーキンソン病予防治療剤 (2013)
  • Inventor(s): 服部信孝、斉木臣二、井本正哉、藤巻貴宏
  • Industrial Property Rights Holder: 服部信孝、斉木臣二、井本正哉、藤巻貴宏
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-25