Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra and movement disorder including tremor or shaking, stiff muscles and achiness, limited movement, and difficulty with balance. The pathogenesis of PD remains unclear and the effective drugs to cure PD have not been found.
α-synuclein is a major component of Lewy bodies observed in the PD patients. It has shown that increasing amount of α-synuclein is an important factor in pathogenic progression of sporadic/familial PD, so controlling the expression of α-synuclein may be a target of therapy for PD.
To identify the small molecules that down-regulate α-synuclein, we employed BAC clone that contains theα-syn genes and its expression regulatory regions, and inserted the secretory luciferase into this BAC clone. Next, we generated the stable SH-SY5Y cells that express the construct. By using these cell lines, we screened the FDA-approved small molecules and found the several hit molesules that down-regulate α-synuclein. We also revealed one of the molecular mechanism of α-synuclein down-regulation by these molecules. In this poster, we will report and discuss the ongoing process of our HTS.