A Perspective on Interdicting in Protein Misfolding for Therapeutic Drug Design: Modulating the Formation of Nonlocal Contacts in α-Synuclein as a Strategy against Parkinson’s Disease

In recent work we proposed that interdiction in the earliest contact-formation events along the folding pathway of key viral proteins could provide a novel avenue for therapeutic drug design. In this Perspective we explore the potential applicability of the protein folding interdiction strategy in the realm of neurodegenerative diseases with a specific focus on synucleinopathies. In order to fulfill this goal we review the interdiction proposal and its practical challenges, and we present new results concerning design strategies for possible peptide drugs that could be useful in preventing α-synuclein aggregation.