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

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 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.