The increase in Parkinson's disease is a social problem in the face of an aging society; however, no fundamental therapeutics has been developed. To approach the etiology of Parkinson's disease and develop therapeutics, we elucidated the mechanism of dopaminergic neurodegeneration as well as a novel regulatory system for neuronal function and conducted a pharmacological analysis of therapeutics using novel drug targets. In detail, we revealed a novel mechanism that tyrosine hydroxylase, a rate-limiting enzyme of dopamine biosynthesis, is lost in dopaminergic neuron selectively and discovered novel drug targets to recover the reduced-dopamine biosynthesis. We further unveiled a mechanism for the α-synuclein uptake into dopaminergic neurons and its propagation, the pathogenesis of Parkinson's disease. These findings suggest preventive and therapeutic applications for Parkinson's disease. Based on these discoveries, we will introduce the overcoming of Lewy body diseases, including Parkinson's disease, and research updates for drug discovery also perspectives.