Autophagy activating drug repurposing based on context-specific network for Parkinson’s disease

Background: Parkinson's disease (PD) is a major long-term degenerative disease that affects the motor system. Parkinson's disease has been increasing over the past 30 years, despite ongoing research and efforts at drug development. The reason is that previous drug development for Parkinson's disease has mainly focused on recovering dopamine levels, which only provides short-term relief. The treatment of PD requires a fundamental approach to treatment. Recent studies prove that misfolded protein aggregation causes mitochondria dysfunction and neuroinflammation so the elimination of the misfolded protein should offer an effective long-term treatment for Parkinson's disease. A promising mechanism to eliminate the misfolded protein is autophagy. Results: We developed a pipeline to identify autophagy-inducing candidate drugs for Parkinson's disease based on Parkinson's disease-specific network and the relationship between drug targets and core autophagy genes. We found 3 autophagy-related genes using RWR algorithm and six drug-repurposing candidates to PD. Conclusions: Our drug repurposing pipeline provides that candidate drugs that show a notable possibility for fundamental PD treatment by activating the autophagy mechanism.