Microglial NLRP3 Inflammasomes in Alzheimer’s Disease Pathogenesis: From Interaction with Autophagy/Mitophagy to Therapeutics

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Language: Английский

Pathogenesis and therapeutic applications of microglia receptors in Alzheimer’s disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 14, 2025

Microglia, the resident immune cells of central nervous system, continuously monitor brain’s microenvironment through their array specific receptors. Once brain function is altered, microglia are recruited to sites perform functions, including phagocytosis misfolded proteins, cellular debris, and apoptotic maintain homeostasis. When toxic substances overproduced, over-activated produce large amounts pro-inflammatory cytokines, which induce chronic inflammatory responses lead neurotoxicity. Additionally, can also protect neuronal microglia-neuron crosstalk. Microglia receptors important mediators for receive external stimuli, regulate functional state microglia, transmit signals between cells. In this paper, we first review role microglia-expressed in pathogenesis treatment Alzheimer’s disease; moreover, emphasize complexity targeting therapeutic interventions neurodegenerative disorders inform discovery new biomarkers development innovative therapeutics

Language: Английский

Microglial repopulation alleviates surgery‐induced neuroinflammation and cognitive impairment in a ZEB1‐dependent manner

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 7, 2025

Microglia play a crucial role in postoperative cognitive dysfunction (POCD). This study investigated the effects of microglial depletion and subsequent repopulation on POCD its underlying mechanisms. An aged mouse model was induced by partial hepatectomy, colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 administered to facilitate repopulation. Neutrophil involvement assessed with anti-Ly6G antibodies, while ZEB1 manipulated through shRNA knockdown lentiviral overexpression BV2 cell line. A TGF-β1 neutralizing antibody employed elucidate relationship between downstream pathways. The results indicated that alone did not reverse impairments. However, significantly reduced neutrophil infiltration improved function post-surgery. improvement correlated upregulation microglia, which decreased CXCL1 production astrocytes via signaling, thereby reducing migration hippocampus. These findings suggest repopulation, dependent effectively alleviates neuroinflammation, reduces infiltration, enhances function, highlighting microglia as promising target for prevention treatment POCD.

Language: Английский