ID 11761
File
Authors
Fukui, Naoya Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University
Yamamoto, Hanae Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University
Miyabe, Moe Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University
Aoyama, Yuki Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University
Hongo, Kunihiro Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University / Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University / Center for Research on Green Sustainable Chemistry, Tottori University Researchers DB KAKEN
Mizobata, Tomohiro Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University / Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University / Center for Research on Green Sustainable Chemistry, Tottori University Researchers DB KAKEN
Kawahata, Ichiro Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
Yabuki, Yasushi Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
Shinoda, Yasuharu Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
Fukunaga, Kohji Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
Kawata, Yasushi Department of Chemistry and Biotechnology, Faculty of Engineering/Graduate School of Engineering, Tottori University / Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University / Center for Research on Green Sustainable Chemistry, Tottori University Researchers DB KAKEN
Abstract
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. In order 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. Since 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.
Publisher
Elsevier
Content Type
Journal Article
Link
ISSN
00219258
EISSN
1083351X
NCID
AA1202441X
Journal Title
Journal of Biological Chemistry
Volume
296
Published Date
2021-04-20
Publisher-DOI
Text Version
Publisher
Rights
© 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. http://creativecommons.org/licenses/by/4.0/
Citation
Fukui, Naoya. Yamamoto, Hanae. Miyabe, Moe. et al. An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3. Journal of Biological Chemistry. 296, 100663. 2021-04-20.
Department
Faculty of Engineering/Graduate School of Engineering
Language
English
pii
S0021-9258(21)00451-8