Targeted protein degradation for the treatment of Parkinson's disease: Advances and future perspective

Abstract

Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed.

Keywords: Lewy bodies; PROTAC; Parkinson’s disease; Targeted protein degradation; α-Synuclein.