【Introduction】In Parkinson`s disease (PD), α-synuclein (αSyn) accumulation and inclusion triggers dopamine neuronal death and synapse dysfunction in vivo. We previously reported that fatty acid-binding protein 3 (FABP3) is highly expresses in dopaminergic neurons and aggravates αSyn oligomerization when exposure to 1-Methyl-1,2,3,6-tetrahydropiridine (MPTP) in vivo and in vitro. We here discovered FABP3 ligands inhibiting α-synuclein oligomerization induced by arachidonic acid (AA).
【Method 】 FABP ligands were modified from FABP4 inhibitor BMS309403 and assessed their inhibitory action on AA-induced α-synuclein oligomerization using FABP3 and αSyn co-overexpressed Neuron2A cells. αSyn oligomerization levels were measured using western blotting assay and immunohistochemical analyses.
【Summary】AA treatment triggered αSyn oligomerization in Neuro2A cells in FABP3-dependent manner. A potent FABP3 ligand 1 totally blocked αSyn oligomerization and aggregation induced by FAPB3 and AA. In addition, ligands 7 and 8 also elicited inhibition of αSyn oligomerization in Neuro2A cells. Taken together, the new FABP3 ligand is attractive therapeutic candidate for Parkinson and Lewy body diseases.