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&#945;-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson&#8242;s disease and other synucleinopathies. Fatty acids partially regulate &#945;-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased &#945;-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons <i>in vivo</i>. In this study, we newly investigated the importance of FABP3 in &#945;-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^{&#8722;/&#8722;} C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH⁺ neurons from FABP3^+/+ mice take up &#945;-Synuclein monomers while FABP3^{&#8722;/&#8722;} TH⁺ neurons do not. The formation of filamentous &#945;-Synuclein inclusions following treatment with MPP⁺ was observed only in FABP3^+/+, and not in FABP3^{&#8722;/&#8722;} neurons. Notably, detailed morphological analysis revealed that FABP^{&#8722;/&#8722;} 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 &#945;-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson&#8242;s disease.