HTS It strengthens the cor relation and shows the credibility of Bayesian analysis we have performed for establishing this intrinsic functional rela tionship between mRNA and miRNA. Among them, two thirds of functional correlations are from 5 DE miRNAs, miR 137, 153, 218, 376a and Inhibitors,Modulators,Libraries 299 5p. They all changed greater than 2 fold. Since all of them have been reported to be involved in classical neurodegeneration, for instance, miR 376a has been reported to mutate in Huntingtons dis ease brains, miR 299 5p has been reported to be dysregulated in multiple sclerosis brains and more interestingly, all of them have been shown to be dysregu lated in the AD brains. In particular, miR 137, 153 and 218, which can target more than 5 neurodegeneration related pathways, implying their functional relevance to the observations noted in this study.
The miR 137 has been shown to be enriched in neurons, especially within the den tate gyrus and the molecular layer of adult hippocampus and studies have shown that it plays an important role in modulating neuronal cell proliferation and differentiation. Inhibitors,Modulators,Libraries Moreover, it has been shown to be genetically asso ciated with schizophrenia. Recently, it has been shown dysregulated in the CSF of HIVE patients, which is con sistent with the expression of miRNA 137 in the frontal cor tex in our study in HAD patients. In addition, the miR 218 is enriched in hippocampus and altered miR 218 ex pression has been reported in HD and MS brains. The miR 153 has been shown to play important role in AD and PD pathogenesis.
It can downregulate the ex pression of APP protein in vivo, suggesting its possible role in AD pathogenesis. Moreover, it can regulate synu Inhibitors,Modulators,Libraries clein, which is the primary structural components of Lewy bodies, indicating its role in PD pathophysiological process. The genes that correlated to are all involved in several significant pathways discussed above. In particular, SPRED1, MAP2K4 and DIRAS2, they all correlated with 3 out of 3 miRNAs and they all appear to be involved Inhibitors,Modulators,Libraries in MAPK signalling pathway, which strongly indi cate the participation of MAPK pathway in HAD pathogen esis and is consistent with our previous proteomic studies. Although our study is the first comprehensive parallel genome wide mRNA and miRNA profiling of HIV infected human brains, there are still limitations, 1.
In future, a bigger sample size, blood and CSF samples will be needed to fur ther validate these findings, and confirm the clinical value of this findings, 2. These findings are based on the Inhibitors,Modulators,Libraries whole human brain cortex rather than specific cell types due to lack of plausible and effective methodologies for perfect cell separation. Although Laser selleck kinase inhibitor Capture Micro dissection is currently used in studying cell types, there are significant limitations in profiling single cell type, A.