Abstract
Prolyl oligopeptidase (PO) interacts with α-synuclein in vitro. It is a weak interaction that induces a nucleation prone conformation of α-synuclein. PO accelerates aggregation and fibril formation of α-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 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 Parkinsons disease. If these interactions also exist in the human brain, PO may be a target for the treatment of Parkinsons disease and other synucleinopathies. Whether PO also contributes to the normal physiological functions of α-synuclein remains an open question, but there are some intriguing parallels between the proposed functions of both proteins that deserve further investigation.
Keywords: Amyloid, peptidase, neurodegeneration, neurotransmission, Parkinson's disease, prolyl oligopeptidase, synuclein, Synucleinopathies, Multiple system atrophy, Dictyostelium discoidum, Alzheimers disease, Z-pro-prolinal, UAMC-00021, Tubulin
CNS & Neurological Disorders - Drug Targets
Title: Interaction of Prolyl Oligopeptidase with α-Synuclein
Volume: 10 Issue: 3
Author(s): Anne-Marie Lambeir
Affiliation:
Keywords: Amyloid, peptidase, neurodegeneration, neurotransmission, Parkinson's disease, prolyl oligopeptidase, synuclein, Synucleinopathies, Multiple system atrophy, Dictyostelium discoidum, Alzheimers disease, Z-pro-prolinal, UAMC-00021, Tubulin
Abstract: Prolyl oligopeptidase (PO) interacts with α-synuclein in vitro. It is a weak interaction that induces a nucleation prone conformation of α-synuclein. PO accelerates aggregation and fibril formation of α-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 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 Parkinsons disease. If these interactions also exist in the human brain, PO may be a target for the treatment of Parkinsons disease and other synucleinopathies. Whether PO also contributes to the normal physiological functions of α-synuclein remains an open question, but there are some intriguing parallels between the proposed functions of both proteins that deserve further investigation.
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Cite this article as:
Lambeir Anne-Marie, Interaction of Prolyl Oligopeptidase with α-Synuclein, CNS & Neurological Disorders - Drug Targets 2011; 10 (3) . https://dx.doi.org/10.2174/187152711794653878
DOI https://dx.doi.org/10.2174/187152711794653878 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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