Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Western blot has been used to study the time-course effect of the two most popular parkinsonian neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, i.p.) and 6-hydroxydopamine (6-OHDA, intra-substantia nigra), on the expression of several regulators of G-protein signaling (RGS2, 4 and 9) in striatum in rodents. During the few days after MPTP challenge, there was a decline (as expected) in tyrosine hydroxylase expression in the mouse striatum that was accompanied by a decline in RGS9 protein; the latter was specific and did not extend to RGS2 or RGS4 which were resistant to the MPTP challenge. Much the same pattern was observed in rats after 6-OHDA challenge, again, specific to RGS9, although the effect takes a few weeks, rather than a few days, to develop. These results may be helpful for the understanding of molecular mechanism underlying Parkinson's disease (PD) and RGS9 might involve in the striatal function associated with PD.
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PMID:Decreased RGS9 protein level in the striatum of rodents undergoing MPTP or 6-OHDA neurotoxicity. 2056 38

Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors. However, mechanisms underlying LID occurrence are still unclear. Regulator of G-protein signaling RGS9, a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, has been reported participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we compared the rotational responses and AIMs in 6-OHDA lesioned rats with L-DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days whereas control animals received injections of saline. Furthermore, whether sub-chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion rats were also evaluated. As results shown, rotational behavior was not increased significantly, while an obvious AIMs were observed in rats with L-DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition, expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR with striatal extracts increased significantly after L-DOPA/benserazide. These data demonstrate that RGS9 expression can be modulated by sub-chronic L-DOPA/benserazide administration and increased RGS9 expression in striatum may be one of the reasons for the side effects such as dyskinesia induced by L-DOPA therapy.
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PMID:The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model. 2196 45