We previously show that fatty acid-binding protein 3(FABP3)triggers α-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 triggers α-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.

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

Department of Pharmacology,Graduate School of Pharmaceutical Sciences,Tohoku University,Sendai,Japan;Department of Chemistry and Biotechnology,Graduate School of Engineering,Tottori University,Tottori,Japan

中国药理学报（英文版）

[1]An Cheng;Yi-fei Wang;Yasuharu Shinoda;Ichiro Kawahata;Tetsunori Yamamoto;Wen-bin Jia;Hanae Yamamoto;Tomohiro Mizobata;Yasushi Kawata;Kohji Fukunaga-.Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress)[J].中国药理学报（英文版）,2022(03):552-562

anilinonaphthalene,psychosine,oligodendroglia

Fatty,acid,binding,protein,triggers,oligomerization,glial,cells,oligodendrocytes,associated,oxidative,stress,We,previously,that,fatty,FABP3,Syn,accumulation,induces,dopamine,neuronal,death,Parkinson,disease,mouse,model,But,role,FABP7,brain,remains,unclear,In,this,study,investigated,whether,was,involved,synucleinopathies,showed,localized,formed,complex,transfected,U251,human,glioblastoma,treatment,arachidonic,significantly,promoted,induced,aggregation,which,demonstrated,synthetic,ligand,displayed,high,affinity,against,Kd,value,nM,assessed,sulfonic,ANS,assay,improved,survival,via,disrupting,interaction,activation,phospholipase,PLA2,triggered,endogenous,both,KG,1C,precursor,OPCs,decreased,thereby,prevented,This,demonstrates,through,while,inhibit,rescuing,from

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