Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with L-dopa-induced dyskinesia

Fasano, Stefania, Bezard, E., D'Antoni, A., Francardo, V., Indrigo, M., Qin, L., Dovero, S., Cerovic, Milica, Cenci, M. A. and Brambilla, Riccardo 2010. Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with L-dopa-induced dyskinesia. Proceedings of the National Academy of Sciences 107 (50) , pp. 21824-21829. 10.1073/pnas.1012071107

Full text not available from this repository.

Abstract

L-dopa–induced dyskinesia (LID) is a common debilitating complication of dopamine replacement therapy in Parkinson's disease. Recent evidence suggests that LID may be linked causally to a hyperactivation of the Ras–ERK signaling cascade in the basal ganglia. We set out to determine whether specific targeting of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), a brain-specific activator of the Ras–ERK pathway, may provide a therapy for LID. On the rodent abnormal involuntary movements scale, Ras-GRF1–deficient mice were significantly resistant to the development of dyskinesia during chronic l-dopa treatment. Furthermore, in a nonhuman primate model of LID, lentiviral vectors expressing dominant negative forms of Ras-GRF1 caused a dramatic reversion of dyskinesia severity leaving intact the therapeutic effect of l-dopa. These data reveal the central role of Ras-GRF1 in governing striatal adaptations to dopamine replacement therapy and validate a viable treatment for LID based on intracellular signaling modulation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: The National Academy of Sciences of the USA
ISSN: 0027-8424
Last Modified: 06 Jan 2019 23:42
URI: http://orca.cf.ac.uk/id/eprint/22376

Citation Data

Cited 70 times in Google Scholar. View in Google Scholar

Cited 101 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item