RGD Reference Report - Inhibition of Glycogen Synthase Kinase-3ß (GSK-3ß) as potent therapeutic strategy to ameliorates L-dopa-induced dyskinesia in 6-OHDA parkinsonian rats.

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Inhibition of Glycogen Synthase Kinase-3ß (GSK-3ß) as potent therapeutic strategy to ameliorates L-dopa-induced dyskinesia in 6-OHDA parkinsonian rats.
Authors:	Xie, Cheng-long Lin, Jing-Ya Wang, Mei-Hua Zhang, Yu Zhang, Su-fang Wang, Xi-Jin Liu, Zhen-Guo
Citation:	Xie CL, etal., Sci Rep. 2016 Mar 21;6:23527. doi: 10.1038/srep23527.
RGD ID:	13792768
Pubmed:	PMID:26997328 (View Abstract at PubMed)
PMCID:	PMC4800499 (View Article at PubMed Central)
DOI:	DOI:10.1038/srep23527 (Journal Full-text)
Levodopa (L-dopa) is the dominating therapy drug for exogenous dopaminergic substitution and can alleviate most of the manifestations of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). Evidence points towards an involvement of Glycogen Synthase Kinase-3ß (GSK-3ß) in development of LID. In the present study, we found that animals rendered dyskinetic by L-dopa treatment, administration of TDZD8 (2mg/kg) obviously prevented the severity of AIM score, as well as improvement in motor function (P < 0.05). Moreover, the TDZD8-induced reduction in dyskinetic behavior correlated with a reduction in molecular correlates of LID. TDZD8 reduced the phosphorylation levels of tau, DARPP32, ERK and PKA protein, which represent molecular markers of LID, as well as reduced L-dopa-induced FosB mRNA and PPEB mRNA levels in the lesioned striatum. In addition, we found that TDZD8 antidyskinetic properties were overcome by D1 receptor, as pretreatment with SKF38393 (5 mg/kg, 10 mg/kg, respectively), a D1 receptor agonist, blocked TDZD8 antidyskinetic actions. This study supported the hypothesis that GSK-3ß played an important role in the development and expression of LID. Inhibition of GSK-3ß with TDZD8 reduced the development of ALO AIM score and associated molecular changes in 6-OHDA-lesioned rats.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
GSK3B	Human	Drug-Induced Dyskinesia	treatment	ISO	Gsk3b (Rattus norvegicus)	associated with Parkinsonian Disorders	RGD
Gsk3b	Rat	Drug-Induced Dyskinesia	treatment	IMP		associated with Parkinsonian Disorders	RGD
Gsk3b	Mouse	Drug-Induced Dyskinesia	treatment	ISO	Gsk3b (Rattus norvegicus)	associated with Parkinsonian Disorders	RGD

Objects Annotated

Genes (Rattus norvegicus)

Gsk3b (glycogen synthase kinase 3 beta)

Genes (Mus musculus)

Gsk3b (glycogen synthase kinase 3 beta)

Genes (Homo sapiens)

GSK3B (glycogen synthase kinase 3 beta)

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Inhibition of Glycogen Synthase Kinase-3ß (GSK-3ß) as potent therapeutic strategy to ameliorates L-dopa-induced dyskinesia in 6-OHDA parkinsonian rats.