title: Interaction of prolyl oligopeptidase with α-synuclein.
abstract: Prolyl oligopeptidase (PO) interacts with α-syncline in vitro. It is a weak interaction that induces a nucleation prone conformation of α-synuclein. PO accelerates aggregation and fibril formation of α-syncline 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 α-synuclein also interact intracellularly, especially in conditions where the expression of α-synuclein is high. Specific PO inhibitors reduce the number of cells with α-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 α-syncline remains an open question, but there are some intriguing parallels between the proposed functions of both proteins that deserve further investigation.
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp - Campus Drie Eiken, Wilrijk, Belgium. anne-marie.lambeir@ua.ac.be
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
mesh_terms: D006801:Humans; D008968:Molecular Conformation; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000502:physiology*; D051844:alpha-Synuclein / Q000737:chemistry / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases