Gene expression networks involved in neuroinflammation and neurodegeneration

Gene expression networks involved in neuroinflammation and neurodegeneration represent the coordinated transcriptional changes in the central nervous system that drive pathological immune responses and neuronal decay (Kuwano, 2024). These networks are primarily centered in microglia and astrocytes, where they regulate the transition from homeostatic states to disease-associated phenotypes, such as the 'Disease-Associated Microglia' (DAM) or 'Microglial Neurodegenerative' (MGnD) signatures (Int. J. Mol. Sci., 2020). Key hub genes within these networks, including TREM2, TYROBP (DAP12), and SPI1 (PU.1), act as master regulators that integrate signals from misfolded proteins like amyloid-beta and tau to trigger pro-inflammatory cascades (PLOS ONE, 2013). Dysregulation of these networks is a fundamental feature of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis (ALS), where chronic activation leads to the release of neurotoxic cytokines and oxidative stress (J. Med. Res. Case Rep., 2024). Therapeutic interventions aim to 'reset' these networks using small molecules, antibodies targeting hub receptors (e.g., TREM2 agonists), or epigenetic modulators like HDAC inhibitors to restore neuroprotective functions (MDPI, 2024). However, the complexity and redundancy of these networks present significant challenges for achieving precise therapeutic effects without compromising essential immune functions.

Other names

Neuroinflammatory gene networksNeurodegenerative gene expression signaturesMicroglial activation networksDisease-associated microglia (DAM) signatureMicroglial neurodegenerative phenotype (MGnD)Gene co-expression networks

Modulation of master regulators, inhibition of pro-inflammatory signaling, enhancement of phagocytic clearance, and epigenetic reprogramming of glial states.