Fatty acid-binding protein 3 is critical for α-synuclein uptake and mpp+-induced mitochondrial dysfunction in cultured dopaminergic neurons

Ichiro Kawahata, Luc Bousset, Ronald Melki, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinsons disease and other synucleinopathies. Fatty acids partially regulate α-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased α-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in α-Synuclein uptake, 1-methyl-4-phenylpyridinium (MPP+)-induced axodendritic retraction, and mitochondrial dysfunction. To disclose the issues, we employed cultured mesencephalic neurons derived from wild type or FABP3−/− C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH+ neurons from FABP3+/+ mice take up α-Synuclein monomers while FABP3−/− TH+ neurons do not. The formation of filamentous α-Synuclein inclusions following treatment with MPP+ was observed only in FABP3+/+, and not in FABP3−/− neurons. Notably, detailed morphological analysis revealed that FABP−/− neurons did not exhibit MPP+-induced axodendritic retraction. Moreover, FABP3 was also critical for MPP+-induced reduction of mitochondrial activity and the production of reactive oxygen species. These data indicate that FABP3 is critical for α-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinsons disease.

Original languageEnglish
Article number5358
JournalInternational journal of molecular sciences
Volume20
Issue number21
DOIs
Publication statusPublished - 2019 Nov 1

Keywords

  • 1-methyl-4-phenylpyridinium (MPP)
  • Fatty acid-binding protein 3
  • Mitochondria
  • Parkinson’s disease
  • Synucleinopathy
  • α-Synuclein

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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