Interaction of Prolyl Oligopeptidase with α-Synuclein

Prolyl oligopeptidase ( PO) interacts with alpha-synuclein in vitro. It is a weak interaction that induces a nucleation prone conformation of alpha-synuclein. PO accelerates aggregation and fibril formation of alpha-synuclein in a process that can be reversed by specific inhibitors and is also influenced by an impairing mutation in the PO active site. There is evidence that PO and alpha-synuclein also interact intracellularly, especially in conditions where the expression of alpha-synuclein is high. Specific PO inhibitors reduce the number of cells with alpha-synuclein inclusions in a cellular model of Parkinson's disease. If these interactions also exist in the human brain, PO may be a target for the treatment of Parkinson's disease and other synucleinopathies. Whether PO also contributes to the normal physiological functions of alpha-synuclein remains an open question, but there are some intriguing parallels between the proposed functions of both proteins that deserve further investigation.