Elucidation of novel control mechanism and therapeutic target of PD instead of activating known ER-stress signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22716
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Tokyo University of Science, Yamaguchi
• Principal Investigator: noda yasuhiro 山陽小野田市立山口東京理科大学, 薬学部, 助教 (90880336)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: パーキンソン病 / 小胞体ストレス

Outline of Final Research Achievements

An inhibitor of PKR-like endoplasmic reticulum kinase (PERK), GSK2606414 ameliorated SH-SY5Y cell death induced by MPP+ which causes PD-like neuronal cell death. On the other hands, GSK2606414 did not exert protective effects against Staurosporine (an apoptosis inducer) or tunicamycin (an ER-stress inducer) induced cell death. These results suggest that GSK2606414 has specific neuroprotective effect in PD. Furthermore, in in vitro PD model, PERK was not activated. Therefore, it is suggested that GSK2606414 can ameliorate PD pathology without activation of PERK pathway, and it can be a candidate of therapeutic agent of PD.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、PD病態において保護作用を有する化合物が新たに見いだされ、治療薬候補としての応用が期待される。また、今回見いだされたGSK2606414は小胞体ストレスセンサーPERKの阻害剤であるにもかかわらず、PERK非依存的な経路で保護作用を発揮することが示されており、PD病態において未知の因子を修飾し、保護作用を発揮することが示唆されているる。今後の検討によって標的因子の同定を行い、PD病態の新たな治療戦略開発につながることが期待される。