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

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

研究成果: Article査読

4 被引用数 (Scopus)

抄録

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.

本文言語English
ジャーナルActa Pharmacologica Sinica
DOI
出版ステータスAccepted/In press - 2021

ASJC Scopus subject areas

  • 薬理学
  • 薬理学(医学)

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