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Figure 1. Mechanisms and role of Microglial-induced neuroinflammation in triggering AD pathophysiology. The neuroinflammatory pathway begins with the engulfment of amyloid-β peptide by resting microglia. This process activates the NLRP3 inflammasome and NFκB pathways, triggering the maturation of microglia into a proinflammatory M1 phenotype, which in turn stimulates the differentiation of naïve T-cells into TH1 and TH17 cells and facilitates their recruitment across the blood-brain barrier. This cascade leads to increased proinflammatory T-cells, cytokines, chemokines, and ROS within the brain environment, thereby driving the maturation and proliferation of M1 microglia, exacerbating oxidative damage, TFNR-1- and NFκB-mediated necroptosis, and resulting in the intracellular accumulation of pTau proteins. Ultimately, this cascade of events leads to neuronal death and cognitive decline. AD: Alzheimer’s disease; CXCR: C-X-C chemokine receptors; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; NFκB: nuclear factor kappa B; NLRP3: NOD-like receptor family, pyrin domain-containing protein 3; pTau: phosphorylated tau protein; ROS: reactive oxygen species; TNF-α: tumor necrosis factor alpha; TNFR-1: tumor necrosis factor receptor 1.
