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Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy.
dc.contributor.author | Crittenden, Jill R | |
dc.contributor.author | Cantuti Castelvetri, Ippolita | |
dc.contributor.author | Saka, Esen | |
dc.contributor.author | Keller-McGandy, Christine E | |
dc.contributor.author | F. Hernandez, Ledia | |
dc.contributor.author | Kett, Lauren E. | |
dc.contributor.author | Young, Anne B | |
dc.contributor.author | Standaert, David G | |
dc.contributor.author | Graybiel, Ann M | |
dc.date.accessioned | 2024-02-06T10:03:12Z | |
dc.date.available | 2024-02-06T10:03:12Z | |
dc.date.issued | 2009-02-24 | |
dc.identifier.citation | Crittenden, J. R., Cantuti-Castelvetri, I., Saka, E., Keller-McGandy, C. E., Hernandez, L. F., Kett, L. R., Young, A. B., Standaert, D. G., & Graybiel, A. M. (2009). Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2892–2896. https://doi.org/10.1073/pnas.0812822106 | es |
dc.identifier.issn | 0027-8424 | |
dc.identifier.other | https://www.pnas.org/doi/full/10.1073/pnas.0812822106 | es |
dc.identifier.other | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650361/ | es |
dc.identifier.uri | http://hdl.handle.net/20.500.12020/1220 | |
dc.description.abstract | Voluntary movement difficulties in Parkinson's disease are initially relieved by l-DOPA therapy, but with disease progression, the repeated l-DOPA treatments can produce debilitating motor abnormalities known as l-DOPA-induced dyskinesias. We show here that 2 striatum-enriched regulators of the Ras/Rap/ERK MAP kinase signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in proportion to the severity of abnormal movements induced by l-DOPA in a rat model of parkinsonism. In the dopamine-depleted striatum, the l-DOPA treatments produce down-regulation of CalDAG-GEFI and up-regulation of CalDAG-GEFII mRNAs and proteins, and quantification of the mRNA levels shows that these changes are closely correlated with the severity of the dyskinesias. As these CalDAG-GEFs control ERK cascades, which are implicated in l-DOPA-induced dyskinesias, and have differential compartmental expression patterns in the striatum, we suggest that they may be key molecules involved in the expression of the dyskinesias. They thus represent promising new therapeutic targets for limiting the motor complications induced by l-DOPA therapy. | es |
dc.description.sponsorship | This work was supported by the Massachusetts General Hospital/Massachusetts Institute of Technology Morris Udall Center of Excellence in Parkinson’s Disease Research (National Institutes of Health Grant NS38372), National Institute of Child Health and Human Development Grant R01-HD28341, the National Parkinson Foundation, and the Stanley H. and Sheila G. Sydney Fund. | es |
dc.language.iso | en | es |
dc.publisher | National Academy of Sciences | es |
dc.title | Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy. | es |
dc.type | article | es |
dc.identifier.doi | https://doi.org/10.1073/pnas.0812822106 | |
dc.identifier.essn | 1091-6490 | |
dc.issue.number | 8 | es |
dc.journal.title | Proceedings of the National Academy of Sciences (PNAS) | es |
dc.page.initial | 2892 | es |
dc.page.final | 2896 | es |
dc.relation.projectID | National Institutes of Health Grant NS38372, National Institute of Child Health and Human Development Grant R01-HD28341 | es |
dc.rights.accessRights | openAccess | es |
dc.subject.area | Biología Celular y Molecular | es |
dc.subject.area | Ciencias Biomédicas | es |
dc.subject.keyword | ERK | es |
dc.subject.keyword | L-DOPA | es |
dc.subject.keyword | Parkinson’s disease | es |
dc.subject.keyword | Striatum | es |
dc.subject.keyword | Dyskinesia | es |
dc.subject.unesco | 24 Ciencias de la Vida | es |
dc.subject.unesco | 2490 Neurociencias | es |
dc.volume.number | 106 | es |