Regulation of neuroinflammatory signaling pathway in neurodegenerative diseases

Zirui Song

doi:10.54097/ww461e32

Authors

Zirui Song

DOI:

https://doi.org/10.54097/ww461e32

Keywords:

neuroinflammatory signaling pathway; neurodegenerative diseases; TLR; NF-κB; NLRP3; TLR; TREM2.

Abstract

Neuroinflammation directly drives neuronal damage through chronic inflammatory microenvironment, and plays a key regulatory role in neurodegenerative diseases (NDDs). Microglia perceive pathological stimuli through classical pathways such as TLR/NF-κB, NLRP3 inflammatory corpuscles and cGAS-STING, and release pro-inflammatory factors and reactive oxygen species, thus forming a vicious cycle of "inflammation-degeneration". Different NDDs present disease-specific activation patterns: Aβ activates NF-κB and NLRP3 pathways through TLR/TREM2 in Alzheimer's Disease (AD); In Parkinson's disease, α -synuclein triggers MAPK cascade through TLR2; Amyotrophic lateral sclerosis highlights the role of cGAS-STING pathway in sensing cytoplasmic DNA. Multi-channels construct a cooperative regulatory network through positive feedback loop and cross-dialogue, such as the self-strengthening cycle promoted by NF-κB and NLRP3, and the polarization of M1 microglia driven by metabolic reprogramming, which leads to uncontrolled and chronic inflammatory reaction.

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