The α-synuclein (SNCA) gene is a responsible gene for Parkinson's disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in the pathogenesis of PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by a specific silencing such as an allele-specific RNA interference (RNAi); however, there is no method for restoring the SNCA overexpression to a normal level. Here, we show that an atypical RNAi using small interfering RNAs (siRNAs) that confer a moderate level of gene silencing is capable of controlling overexpressed SNCA genes to return to a normal level; named "expression-control RNAi" (ExCont-RNAi). ExCont-RNAi exhibited little or no significant off-target effects in its treated PD patient's fibroblasts that carry SNCA triplication. To further assess the therapeutic effect of ExCont-RNAi, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression, and that siRNAs conferring a moderate level of gene silencing to target genes, which have been abandoned as useless siRNAs so far, might be available for controlling abnormally expressed disease-causing genes without producing adverse effects.
The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.
Guizhou Engineering Research Center for Fruit Crops, Agricultural College, Guizhou University, Guiyang, 550025, People's Republic of China. Electronic address:
Sugar content is an important factor that largely determines fruit quality. 'Fengtang' plum (Prunus salicina Lindl.) is recognized for its high soluble sugar content, and the Sucrose synthase 4 (PsSUS4) functions as the controlling step in sucrose accumulation.
Patients with chronic myeloid leukemia (CML) frequently develop resistance to tyrosine kinase inhibitors such as imatinib. In this study, we explored the role of the insulin-like growth factor 1 (IGF-1) signaling pathway in CML and imatinib resistance. An analysis of IGF-1 gene expression using public databases revealed elevated levels of insulin-like growth factor-binding proteins in patients with chronic-phase CML.
Center for Plant Water-use and Nutrition Regulation and College of JunCao Science and Ecology, Joint International Research Laboratory of Water and Nutrient in Crop, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
White lupin (Lupinus albus L.) produces cluster roots to acquire more phosphorus under phosphorus deficiency. Bacillus amyloliquefaciens SQR9 contributes to plant growth, but whether and how it promotes cluster root formation in white lupin remain unclear.
SP140, a lymphocytic-restricted protein, is an epigenetic reader working as a corepressor of genes implicated in inflammation and orchestrating macrophage transcriptional programs to maintain cellular identity. Reduced SP140 expression is associated both to autoimmune diseases and blood cancers. However, the molecular mechanisms that link SP140 altered protein levels to detrimental effects on the immune response and cellular growth, as well as the interactors through which SP140 promotes gene silencing, remain elusive.
