Title
Prolyl oligopeptidase stimulates the aggregation of α-synuclein Prolyl oligopeptidase stimulates the aggregation of α-synuclein
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Fayetteville, N.Y. ,
Subject
Chemistry
Pharmacology. Therapy
Source (journal)
Peptides. - Fayetteville, N.Y.
Volume/pages
29(2008) :9 , p. 1472-1478
ISSN
0196-9781
ISI
000259346400002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
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