Synucleozid is a potent the SNCA mRNA inhibitor that encodes α-synuclein protein (IC50=1.5 μM), has the potential for the investigation of Parkinson’s disease.

SNCA IRE RNA:1.5 μM

Synucleozid (0.25-1 μM; 24 hours) eliminates α-synuclein preformed fibrils induced cytotoxicity by acting as seeds and recruiting endogenous α-synuclein aggregation. It binds to the A bulge near the base of the IRE hairpin, reducing α-synuclein levels in a dose-dependent manner (IC50: 500 nM), and inhibits α-synuclein protein expression in SH-SY5Y neuroblastoma cells. Synucleozid (100 nM-100 μM; 24 hours) binds to 2-AP-labeled and native IRE RNA with similar affinities, decreasing 2-AP emission (EC50: 2.7 μM), with recovery observed as a function of unlabeled SNCA IRE RNA concentration, yielding a competitive Kd of 1.5 μM. Additionally, Synucleozid (0.25-1 μM; 24 hours) decreases α-synuclein and other proteins with IREs in their mRNA's UTR, such as APP, PrP, Ferritin, and TfR, in a dose-dependent manner. All panels are completed in SH-SY5Y cells, except for PrP protein, which is assessed in Neuro-2A cells.