Downregulated Glia Interplay and Increased miRNA-155 as Promising Markers to Track ALS at an Early Stage.

摘要: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence specific targets and biomarkers compromise the development new therapeutic strategies innovative tools to stratify patients assess their responses treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions spinal cord SOD1 G93A mice, at presymptomatic symptomatic stages identify stage-specific potential targets. Results showed that stage, there are alterations both astrocytes microglia, which comprise decreased expression GFAP S100B upregulation GLT-1, as well reduced CD11b, M2-phenotype markers, set inflammatory mediators. Reduced levels Connexin-43, Pannexin-1, CCL21, CX3CL1 further indicate existence compromised intercellular communication. In contrast, increased markers inflammation became evident, such NF-κB/Nlrp3-inflammasome, Iba1, pro-inflammatory cytokines, M1-polarizion together with M2-phenotypic markers. We also observed upregulation CX3CL1-CX3CR1 axis, microRNAs (miR)-124, miR-125b, miR-146a miR-21. motor neuron number presence reactive GFAP, GLAST characterized this stage. Interestingly, miR-155 downregulation MFG-E8 appear consistent stages. We hypothesize downregulated cellular interplay early may represent neuroprotective mechanisms against inflammation, SOD1 aggregation, ALS onset. The present study identified inflamma-miRNAs, NLRP3-inflammasome, HMGB1, CX3CL1-CX3CR1, Pannexin-1 emerging candidates promising pharmacological therapy.