title: FABP3 protein promotes α-synuclein oligomerization associated with 1-methyl-1,2,3,6-tetrahydropiridine-induced neurotoxicity.
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.
authors.affiliation: From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shioda
authors.affiliation: From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yabuki
authors.affiliation: From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.
authors.forename: Misaki
authors.initials: M
authors.lastname: Onozato
authors.affiliation: the Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.affiliation: From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and kfukunaga@m.tohoku.ac.jp.
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009498:Neurotoxins; D051844:alpha-Synuclein; D016718:Arachidonic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Cell Death; Dopamine; Dopaminergic Neuron; Fatty Acid-binding Protein; Fatty Acid-binding Protein 3; Parkinson Disease; Polyunsaturated Fatty Acid (PUFA); α-Synuclein