Publication
Title
Prolyl oligopeptidase stimulates the aggregation of α-synuclein
Author
Abstract
Despite its thorough enzymological and biochemical characterization the exact function of prolyl oligopeptidase (PO, E.C. 3.4.21.26) remains unclear. The positive effect of PO inhibitors on learning and memory in animal models for amnesia, enzyme activity measurements in patient samples and (neuro)peptide degradation studies link the enzyme with neurodegenerative disorders. The brain protein á-synuclein currently attracts much attention because of its proposed role in the pathology of Parkinson's disease. A fundamental question concerns how the essentially disordered protein is transformed into the highly organized fibrils that are found in Lewy bodies, the hallmarks of Parkinson's disease. Using gel electrophoresis and MALDI TOF/TOF mass spectrometry we investigated the possibility of á-synuclein as a PO substrate. We found that in vitro incubation of the protein with PO did not result in truncation of full-length á-synuclein. Surprisingly, however, we found an acceleration of the aggregation process of á-synuclein using turbidity measurements that was reversed by specific inhibitors of PO enzymatic activity. If PO displays this activity also in vivo, PO inhibitors might have an effect on neurodegenerative disorders through a decrease in the aggregation of á-synuclein.
Language
English
Source (journal)
Peptides. - Fayetteville, N.Y.
Publication
Fayetteville, N.Y. : 2008
ISSN
0196-9781
Volume/pages
29:9(2008), p. 1472-1478
ISI
000259346400002
Full text (Publishers DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 15.01.2009
Last edited 16.05.2017
To cite this reference