Alpha-synuclein aggregations are promoted by fatty acid-binding protein 3 and arachidonic acid

[Speaker] Yasuharu Shinoda:1
[Co-author] An Cheng:1, Shuto Hachinohe:1, Kohji Fukunaga:1
1:Department of Pharmacology, Tohoku University Graduate School of Pharmaceutical Sciences, Japan

Background: Abnormal aggregation of alpha-synuclein in the central nervous system is a hallmark of Parkinson's disease (PD) and dementia with lewy body (DLB). We recently defined that MPTP-induced aggregations of alpha-synuclein and motor deficits are diminished in fatty acid-binding protein 3 (FABP3) gene-ablated mice (Shioda et al., J Biol Chem, 2014). In the present study, we analyzed effects of FABP3 on alpha-synuclein aggregations in neuroblastoma Neuro-2A cells and in vitro with recombinant proteins.
Method: Neuro-2A cells were transfected with gene plasmids encoding alpha-synuclein and FABP3. Cells were lysed, and aggregations were analyzed using immunoblotting under non-denatured condition. Cells were also treated with arachidonic acid (AA) which is reported to induce aggregations of alpha-synuclein. Recombinant proteins were incubated at 37°C for 2 hr, and aggregations were analyzed.
Results & Discussion: Co-expression of FABP3 with alpha-synuclein in Neuro-2A cell promoted alpha-synuclein aggregations which were appeared as high molecular weight proteins in non-denatured gels. Furthermore, AA-induced aggregations of alpha-synuclein were aggravated by co-expression of FABP3. Similar aggravation was also observed by incubation of recombinant alpha-synuclein with FABP3 proteins. These results suggest that poly-unsaturated fatty acid like AA not only induced alpha-synuclein aggregation, but also enhances its aggregation through FABP3 in neurodegenerative disorders.

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