Figure S1 - Human α4β2 Nicotinic Acetylcholine Receptor as a Novel Target of Oligomeric α-Synuclein

Effects of pretreatment of oligomeric amyloid (Aβ1-42) on α-synuclein-induced inhibition of human α4β2-nAChRs heterologously expressed in SH-EP1 cell line. We found that after 10 min pre-treatment with 1 nM oligomeric Aβ1-42, 3 µM nicotine (around EC50 concentration)-induced inward current was reduced (Figure S1A, blue trace). Thereafter, we immediately added 10 nM α-synuclein (in the continuous presence of 1 nM Aβ1-42) for 10 min, and then tested nicotinic response. However, we did not observe further reduction of nicotine-induced inward current (Figure S1A, red trace). Statistic analysis showed that Aβ1-42 pre-treatment significantly reduced both peak and steady-state components of nicotine-induced-whole-cell current (Figure S1B, n = 6, pp>0.05 between Aβ1-42 and α-synuclein treated group), indicated as no significance (NS) in the figure. These results suggest that both oligomeric molecules of Aβ1-42 and α-synuclein likely bind to a common negative allosteric site to reduce human α4β2-nAChR function. (DOC)