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)

Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The open field tasks and Morris water maze were used to assess the effect of CTL on anxiety-like behavioral and cognitive impairment after I/R. Western blotting were performed to examine the expression of related proteins, and HE-staining was used to detect the percentage of neuronal death in the hippocampal CA1 region. Here we found that CTL significantly improved cognitive deficits and the behavior of rats in Morris water maze and open field tasks (P<0.05). HE staining results showed that CTL could significantly protect CA1 neurons against cerebral I/R (P<0.05). Additionally, Akt1 phosphorylation levels were evidently up-regulated (P<0.05), while the activation of JNK3, which is an important contributor to I/R-induced neuron apoptosis, was reduced by CTL after I/R (P<0.05), and caspase-3 levels were also decreased by CTL treatment. Furthermore, all of CTL's protective effects were reversed by LY294002, which is a PI3K/Akt1 inhibitor. Taken together, our results suggest that CTL could protect hippocampal neurons and ameliorate the impairment of learning/memory abilities and locomotor/ exploratory activities in ischemic stroke via a PI3K-Akt1/JNK3/caspase-3 dependent mechanism.
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PMID:Neuroprotection of Cilostazol against ischemia/reperfusion-induced cognitive deficits through inhibiting JNK3/caspase-3 by enhancing Akt1. 2776 87

Effect of PI3K/Akt/mTOR signaling pathway on the expression of JNK3 in Parkinsonian rats was investigated. A total of 200 rats were used for Parkinson's disease (PD) modeling and 180 models were successfully established. Rats were randomly divided into four groups including A, B, C, and D, 45 in each group. Group A was control group and no inhibitor was given. Group B was given PI3K inhibitor LY294002. Group C was given rapamycin inhibitor rapamycin; and group D was given inhibitor LY294002 and inhibitor rapamycin. JNK3 mRNA expression was detected by RT-qPCR and expression of p-mTOR protein and JNK3 protein was detected by western blot analysis. Expression level of JNK3 mRNA and protein in groups C and D was significantly lower than that in group B (P<0.01). Expression level of JNK3 mRNA and protein in group D was significantly lower than that in group C (P<0.01). Relative expression level of p-mTOR protein in groups C and D was significantly lower than that in group B (P<0.01). Relative expression level of JNK3 protein in group D was significantly lower than that in group C (P<0.01). Pearson's correlation analysis showed that expression of JNK3 mRNA was positively correlated with the expression of JNK3 protein and Pearson's correlation coefficient was 0.98 (P<0.01). There was also a positive correlation between the expression of JNK3 mRNA and the expression of p-mTOR protein and Pearson's correlation coefficient was 0.95 (P<0.01). Expression of JNK3 protein was positively correlated with the expression of p-mTOR protein, and the Pearson's correlation coefficient was 0.93 (P<0.01). Inhibition of PI3K/Akt/mTOR signaling pathway is negatively correlated with the expression of JNK3. Inhibition of PI3K-Akt-mTOR signaling pathway leads to a decrease in the expression of JNK3, which protects dopaminergic neurons and improves PD.
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PMID:Effect of PI3K/Akt/mTOR signaling pathway on JNK3 in Parkinsonian rats. 3078 48


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