Microglial double stranded DNA accumulation induced by DNase II deficiency drives neuroinflammation and neurodegeneration.

ABSTRACT:

Background

Deoxyribonuclease 2 (DNase II) is pivotal in the clearance of cytoplasmic double stranded DNA (dsDNA). Its deficiency incurs DNA accumulation in cytoplasm, which is a hallmark of multiple neurodegenerative diseases. Our previous study showed that neuronal DNase II deficiency drove tau hyperphosphorylation and neurodegeneration (Li et al., Transl Neurodegener 13:39, 2024). Although it has been verified that DNase II participates in type I interferons (IFN-I) mediated autoinflammation and senescence in peripheral systems, the role of microglial DNase II in neuroinflammation and neurodegenerative diseases such as Alzheimer's disease (AD) is still unknown.

Methods

The levels of microglial DNase II in triple transgenic AD mice (3xTg-AD) were measured by immunohistochem

SUBMITTER: Li LJ 

PROVIDER: S-EPMC11745000 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature