Fig. 1: Dynamic microglial activation programs and signaling networks in Alzheimer’s dis...

Dynamic microglial activation programs and signaling networks in Alzheimer’s disease (AD). Under physiological conditions, microglia exist in a state of homeostatic surveillance, which is essential for maintaining synapses and monitoring the immune system. In response to amyloid-β accumulation, tau pathology, and cellular stress, microglia undergo dynamic transcriptional and functional reprogramming rather than fixed polarization. Pro-inflammatory microglial activation programs, driven by Toll-like receptors (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) (JAK/STAT) signaling, promote cytokine release, oxidative stress, and neuronal injury when persistently engaged. Conversely, repair-associated and phagocytic microglial programs regulated by AMP-activated protein kinase (AMPK), phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor g

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