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J Biol Chem. 2014 Jul 4;289(27):18957-65. doi: 10.1074/jbc.M113.527341. Epub 2014 May 22.

FABP3 protein promotes α-synuclein oligomerization associated with 1-methyl-1,2,3,6-tetrahydropiridine-induced neurotoxicity.

Author information

  • 1From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.
  • 2the Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan.
  • 3From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and kfukunaga@m.tohoku.ac.jp.

Abstract

α-Synuclein (αSyn) 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 αSyn in the substantia nigra pars compacta, and αSyn 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 αSyn 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, αSyn oligomerization in DA neurons is likely aggravated by AA through FABP3 in Parkinson disease pathology.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

KEYWORDS:

Cell Death; Dopamine; Dopaminergic Neuron; Fatty Acid-binding Protein; Fatty Acid-binding Protein 3; Parkinson Disease; Polyunsaturated Fatty Acid (PUFA); α-Synuclein

PMID:
24855640
[PubMed - indexed for MEDLINE]
PMCID:
PMC4081935
[Available on 2015-07-04]
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