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Abnormal structure-specific peptide transmission and processing in a primate model of Parkinson's disease and L-DOPA-induced dyskinesia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2014 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 62, 307-312 p.Article in journal (Refereed) Published
Abstract [en]

A role for enhanced peptidergic transmission, either opioidergic or not, has been proposed for the generation of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) on the basis of in situ hybridization studies showing that striatal peptidergic precursor expression consistently correlates with LID severity. Few studies, however, have focused on the actual peptides derived from these precursors. We used mass-spectrometry to study peptide profiles in the putamen and globus pallidus (internalis and externalis) collected from 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine treated macaque monkeys, acutely or chronically treated with L-DOPA. We identified that parkinsonian and dyskinetic states are associated with an abnormal production of proenkephalin-, prodynorphin- and protachykinin-1-derived peptides in both segments of the globus pallidus. Moreover, we report that peptidergic processing is dopamine-state dependent and highly structure-specific, possibly explaining the failure of previous clinical trials attempting to rectify abnormal peptidergic transmission.

Place, publisher, year, edition, pages
2014. Vol. 62, 307-312 p.
Keyword [en]
Parkinson's disease, Mass spectrometry, Peptides, L-DOPA-induced dyskinesia, Primate, MPTP
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-220292DOI: 10.1016/j.nbd.2013.10.016ISI: 000330553600028OAI: oai:DiVA.org:uu-220292DiVA: diva2:706027
Note

De två första författarna delar första författarskapet.

Available from: 2014-03-18 Created: 2014-03-12 Last updated: 2017-12-05Bibliographically approved

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Nilsson, AnnaWadensten, HenrikAndrén, Per E.

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