| First Author | Shioda N | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 27 | Pages | 18957-65 |
| PubMed ID | 24855640 | Mgi Jnum | J:216023 |
| Mgi Id | MGI:5607497 | Doi | 10.1074/jbc.M113.527341 |
| Citation | Shioda N, et al. (2014) FABP3 protein promotes alpha-synuclein oligomerization associated with 1-methyl-1,2,3,6-tetrahydropiridine-induced neurotoxicity. J Biol Chem 289(27):18957-65 |
| abstractText | alpha-Synuclein (alphaSyn) accumulation in dopaminergic (DA) neurons is partly regulated by long-chain polyunsaturated fatty acids. We found that fatty acid-binding protein 3 (FABP3, H-FABP), a factor critical for arachidonic acid (AA) transport and metabolism in brain, is highly expressed in DA neurons. Fabp3 knock-out (Fabp3(-/-)) mice were resistant to 1-methyl-1,2,3,6-tetrahydropiridine-induced DA neurodegeneration in the substantia nigra pars compacta and showed improved motor function. Interestingly, FABP3 interacted with alphaSyn in the substantia nigra pars compacta, and alphaSyn accumulation following 1-methyl-1,2,3,6-tetrahydropiridine treatment was attenuated in Fabp3(-/-) compared with wild-type mice. We confirmed that FABP3 overexpression aggravates AA-induced alphaSyn oligomerization and promotes cell death in PC12 cells, whereas overexpression of a mutant form of FABP3 lacking fatty-acid binding capacity did not. Taken together, alphaSyn oligomerization in DA neurons is likely aggravated by AA through FABP3 in Parkinson disease pathology. |
