Fatty acid-binding protein 7 triggers α-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
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Article Neuropharmacology
• 页码范围: 552-562
• 页数: 11页
• 语种: 英文

摘要

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.