Fatty acid-binding protein 7 triggersα-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress  

作　　者：An Cheng Yi-fei Wang Yasuharu Shinoda Ichiro Kawahata Tetsunori Yamamoto Wen-bin Jia Hanae Yamamoto Tomohiro Mizobata Yasushi Kawata Kohji Fukunaga 

机构地区：[1]Department of Pharmacology,Graduate School of Pharmaceutical Sciences,Tohoku University,Sendai,Japan [2]Department of Chemistry and Biotechnology,Graduate School of Engineering,Tottori University,Tottori,Japan

出　　处：《Acta Pharmacologica Sinica》2022年第3期552-562,共11页中国药理学报（英文版）

基　　金：This work was supported in part by the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development(JP17dm0107071,JP18dm0107071,JP19dm0107071,and JP20dm0107071;awarded to KF).

摘　　要：We previously show that fatty acid-binding protein 3(FABP3)triggersα-synuclein(Syn)accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model.But the role of fatty acid-binding protein 7(FABP7)in the brain remains unclear.In this study we investigated whether FABP7 was involved in synucleinopathies.We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells,and treatment with arachidonic acid(100 M)significantly promoted FABP7-induced Syn aggregation,which was associated with cell death.We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid(ANS)assay;ligand 6 improved U251 cell survival via disrupting the FABP7–Syn interaction.We showed that activation of phospholipase A2(PLA2)by psychosine(10 M)triggered oligomerization of endogenous Syn and FABP7,and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells(OPCs).FABP7 ligand 6(1 M)significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death.This study demonstrates that FABP7 triggersα-synuclein oligomerization through oxidative stress,while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation,thereby rescuing glial cells and oligodendrocytes from cell death.

关 键 词：SYNUCLEINOPATHIES α-synuclein oligomerization fatty acid binding protein 7 arachidonic acid psychosine cell death 

分 类 号：R96[医药卫生—药理学]