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Pramipexole reduces phosphorylation of α-Synuclein at Serine-129

Chau, KY; Cooper, JM; Schapira, AH; (2013) Pramipexole reduces phosphorylation of α-Synuclein at Serine-129. Journal of Molecular Neuroscience , 51 pp. 573-580. 10.1007/s12031-013-0030-8. Green open access

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Abstract

α-Synuclein is a central component of the pathogenesis of Parkinson's disease (PD). Phosphorylation at serine-129 represents an important post-translational modification and constitutes the major form of the protein in Lewy bodies. Several kinases have been implicated in the phosphorylation of α-synuclein. The targeting of kinase pathways as a potential to influence the pathogenesis of PD is an important focus of attention, given that mutations of specific kinases (LRRK2 and PINK1) are causes of familial PD. Pramipexole (PPX) is a dopamine agonist developed for the symptomatic relief of PD. Several in vitro and in vivo laboratory studies have demonstrated that PPX exerts neuroprotective properties in model systems of relevance to PD. The present study demonstrates that PPX inhibits the phosphorylation of α-synuclein and that this is independent of dopamine receptor activation. PPX blocks the increase in phosphorylated α-synuclein induced by inhibition of the ubiquitin proteasomal system. The phosphorylation of α-synuclein occurs in part at least through casein kinase 2, and PPX in turn reduces the phosphorylation of this enzyme, thereby inhibiting its activity. Thus, PPX decreases the phosphorylation of α-synuclein, and this mechanism may contribute to its protective properties in PD models.

Type: Article
Title: Pramipexole reduces phosphorylation of α-Synuclein at Serine-129
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12031-013-0030-8
Publisher version: http://dx.doi.org/10.1007/s12031-013-0030-8
Language: English
Additional information: © The Author(s) 2013. This article is published with open access at Springerlink.com This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1393820
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