PU.1 dictates β-amyloid-induced TREM2 expression upregulation in microglia in a transgenic model of Alzheimer’s disease DOI Creative Commons
Zhen Wei, Xiaodong Pan, Xiaoli Cui

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: May 1, 2025

Introduction Microglial dysfunction is characteristic of Alzheimer’s disease (AD), with triggering receptor expressed on myeloid cells 2 (TREM2) and transcription factor PU.1 playing crucial roles. However, the relationship between TREM2 remains unclear. Methods We investigated expression patterns in 5×FAD mouse AD model. Experimental approaches included quantitative PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, luciferase reporter assays to examine interaction TREM2. The phagocytic function microglial was evaluated using Aβ42 Nile red fluorescent microsphere phagocytosis assays. Results significantly correlated brain β-amyloid (β) deposition. directly interacted promoter region, promoting its potently impacting phagocytosis. overexpression amplified expression, while knockdown reduced it. Discussion Our findings reveal a novel regulatory mechanism where modulates activated microglia during progression. These insights highlight potential as therapeutic targets treatment.

Language: Английский

PU.1 dictates β-amyloid-induced TREM2 expression upregulation in microglia in a transgenic model of Alzheimer’s disease DOI Creative Commons
Zhen Wei, Xiaodong Pan, Xiaoli Cui

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: May 1, 2025

Introduction Microglial dysfunction is characteristic of Alzheimer’s disease (AD), with triggering receptor expressed on myeloid cells 2 (TREM2) and transcription factor PU.1 playing crucial roles. However, the relationship between TREM2 remains unclear. Methods We investigated expression patterns in 5×FAD mouse AD model. Experimental approaches included quantitative PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, luciferase reporter assays to examine interaction TREM2. The phagocytic function microglial was evaluated using Aβ42 Nile red fluorescent microsphere phagocytosis assays. Results significantly correlated brain β-amyloid (β) deposition. directly interacted promoter region, promoting its potently impacting phagocytosis. overexpression amplified expression, while knockdown reduced it. Discussion Our findings reveal a novel regulatory mechanism where modulates activated microglia during progression. These insights highlight potential as therapeutic targets treatment.

Language: Английский

Citations

0