Cognitive impairment is one of the primary features of vascular dementia (VD). However, the specific mechanism underlying the regulation of cognition function in VD is not completely understood. The present study aimed to explore the effects of microRNA (miR)-150 on VD. To determine the effects of miR-150 on cognitive function and hippocampal neurons in VD model rats, rats were subjected to intracerebroventricular injections of miR-150 antagomiR. The Morris water maze test results demonstrated that spatial learning ability was impaired in VD model rats compared with control rats. Moreover, compared with antagomiR negative control (NC), miR-150 antagomiR alleviated cognitive impairment and enhanced memory ability in VD model rats. The triphenyltetrazolium chloride, Nissl staining and immunohistochemistry results further demonstrated that miR-150 knockdown improved the activity of hippocampal neurons in VD model rats compared with the antagomiR NC group. To validate the role of miR-150 in neurons in vitro , the PC12 cell line was used. The flow cytometry and Hoechst 33342/PI double staining results indicated that miR-150 overexpression significantly increased cell apoptosis compared with the mimic NC group. Moreover, the dual-luciferase reporter gene assay results indicated that miR-150 targeted HOXA1 and negatively regulated HOXA1 expression. Therefore, the present study indicated that miR-150 knockdown ameliorated VD symptoms by upregulating HOXA1 expression in vivo and in vitro .
This study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.
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