PMX 205

Complement protein C5a enhances the β-amyloid-induced neuro-inflammatory response in microglia in Alzheimer’s disease

Objective: The dysregulation of neuro-inflammation is among the features of the pathogenesis of Alzheimer’s (AD). Over-expression of complement proteins co-localizes with neurofibrillary tangles, therefore indicating that the complement system may engage in neuro-inflammation. Here, we report the influence of complement activation around the neuro-inflammation utilizing a microglial cell line.

Methods: first, we performed a cytotoxic assay while using microglial cells BV-2. Second, after management of BV-2 cells with Aß42 and/ or C5a, the anaphylatoxin produced from C5, we determined the expression quantity of a pro-inflammatory factors TNF-a, IL-1ß, and IL-6. Finally, we explored whether this neuroinflammatory response was mediated by JAK/ STAT3 signaling.

Results: C5a had an improved impact on the neural cell viability of BV-2 cells given Aß42. Additionally, C5a also elevated the Aß-caused neuro-inflammatory response, which effects were blocked through the C5aR antagonist, PMX205. Finally, we shown the neuro-inflammatory responses caused by Aß and C5a were mediated through JAK/STAT3 signaling. By blocking this path by having an antagonist, AG490, the expression of TNF-a, IL-1ß, and IL-6 was alleviated.

Conclusion: The complement protein C5a could embellish the Aß-caused neuroinflammatory PMX 205 response in microglia, and C5aR can be a potential therapeutic tool for AD treatment.