An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

Naoya Fukui, Hanae Yamamoto, Moe Miyabe, Yuki Aoyama, Kunihiro Hongo, Tomohiro Mizobata, Ichiro Kawahata, Yasushi Yabuki, Yasuharu Shinoda, Kohji Fukunaga, Yasushi Kawata

研究成果: Article査読

2 被引用数 (Scopus)

抄録

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson’s disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. To characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3–αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Because this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3–αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson’s disease.

本文言語English
論文番号100663
ジャーナルJournal of Biological Chemistry
296
DOI
出版ステータスPublished - 2021 1 1

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

フィンガープリント

「An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル