| First Author | Kawahata I | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 21 | PubMed ID | 31661838 |
| Mgi Jnum | J:292847 | Mgi Id | MGI:6451213 |
| Doi | 10.3390/ijms20215358 | Citation | Kawahata I, et al. (2019) Fatty Acid-Binding Protein 3 is Critical for alpha-Synuclein Uptake and MPP(+)-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons. Int J Mol Sci 20(21):5358 |
| abstractText | alpha-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson's disease and other synucleinopathies. Fatty acids partially regulate alpha-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased alpha-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in alpha-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 alpha-Synuclein monomers while FABP3(-/-) TH(+) neurons do not. The formation of filamentous alpha-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 alpha-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson's disease. |
