Up-regulation of IL-1 signaling pathway enhances gene expression of transcription factors (Jun, Junb, Jund, and Fos)

Preventing he accumulation of Beta-amyloid (A) plaques has been explored as main treatment of Alzheimers disease. Microglial deletion of the gene encoding -site APP cleaving enzyme (BACE-1), an important enzyme facilitating the formation of A, leads to the transition from homeostatic microglia to stage 1 disease-associated microglia (DAM-1) while preventing DAM-1 from further converting into stage 2 disease-associated microglia (DAM-2). Therefore, investigating the pathway of this process can be insight of targeted drug development. In the review part of this paper, the Interleukin-1 (IL-1) pathway is discussed. Based on previous research, a proposal hypothesizing that the activation of the IL-1 signaling pathway enhances the activity of TF and leads to the up-regulation of TF gene expression is designed. The goal is to prove that the up-regulation of IL-1 Signaling pathway can enhance the gene expression of Transcription factors including Jun, Junb, Jund, and Fos, therefore stabilizing the microglia at the stage of DAM-1. Based on the expected experimental results of this study, targeted drugs such as Soluble Type II receptor of Interleukin-1 (sIL-1R2) inhibitors can be developed for AD treatment.