Development of novel therapeutics for Parkinson disease by FABP3 ligands
| Project/Area Number |
15H06036
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-08-28 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | パーキンソン病 / α-シヌクレイン / FABP3 / 薬理学 / 薬学 / 脳神経疾患 / 神経科学 |
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| Outline of Final Research Achievements |
α-synuclein is one of major components in lewy bodies and its aggregates promotes neurodegeneration and cell death in dopaminergic neurons, thereby triggering Parkinson disease. Fatty acid binding protein 3 (FABP3) aggravates MPTP-induced α-synuclein oligomerizations in mouse dopaminergic neurons. In the present study, we investigated whether FABP3 ligands prevent α-synuclein oligomerizations and motor impairments in Parkinson models. In vitro assay, FABP3 ligands significantly inhibited MPP+-induced α-synuclein oligomerizations in both α-synuclein and FABP3 over-expressed PC12 cells. In addition, oral administration of FABP3 ligands significantly prevented α-synuclein oligomerizations and cell death in dopaminergic neurons in the substantia nigra, thereby improving motor impairments seen in animal model of Parkinson disease. Taken together, those results suggest that FABP3 ligands may be attractive candidate of novel therapeutics for Parkinson disease.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Trans-fatty acids promote proinflammatory signaling and cell death by stimulating the apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway.2017
Author(s)
Hirata, Y., Takahashi, M., Kudoh, Y., Kano, K., Kawana, H., Makide, K., Shinoda, Y., Yabuki, Y., Fukunaga, K., Aoki, J., Noguchi, T., Matsuzawa, A.
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Journal Title
J. Biol. Chem.
Volume: 印刷中
Issue: 20
Pages: 8174-8185
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pharmacological properties of SAK3, a novel T-type voltage-gated Ca2+ channel enhancer.2017
Author(s)
Yabuki Y, Matsuo K, Izumi H, Haga H, Yoshida T, Wakamori M, Kakehi A, Sakimura K, Fukuda T, Fukunaga K.
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Journal Title
Neuropharmacology.
Volume: 117
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy.2016
Author(s)
Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh JZ, Sakagami H, Narahashi T, Fukunaga K.
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Journal Title
Mol Psychiatry.
Volume: 印刷中
Issue: 2
Pages: 211-221
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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