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Open AccessArticle

Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP+-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons

1
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
2
CEA, Institut François Jacob (MIRcen) and CNRS, Laboratory of Neurodegenerative Diseases, 18 Route du Panorama, 92265 Fontenay-aux-Roses, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5358; https://doi.org/10.3390/ijms20215358
Received: 28 September 2019 / Revised: 23 October 2019 / Accepted: 25 October 2019 / Published: 28 October 2019
α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson′s 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 Parkinson′s disease. View Full-Text
Keywords: fatty acid-binding protein 3; α-Synuclein; 1-methyl-4-phenylpyridinium (MPP+); mitochondria; synucleinopathy; Parkinson’s disease fatty acid-binding protein 3; α-Synuclein; 1-methyl-4-phenylpyridinium (MPP+); mitochondria; synucleinopathy; Parkinson’s disease
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Kawahata, I.; Bousset, L.; Melki, R.; Fukunaga, K. Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP+-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons. Int. J. Mol. Sci. 2019, 20, 5358.

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