Alzheimer's alphabet soup: Find the letters "Z-DNA-ZBP1-RIPK1"

Immunity. 2025 Oct 14;58(10):2367-2369. doi: 10.1016/j.immuni.2025.09.010.

Abstract

Neuroinflammation contributes to Alzheimer's disease (AD), but the molecules and pathways that initiate inflammation are unclear. In this issue of Immunity, Song et al. demonstrate that ZBP1-RIPK1 signaling in microglia can drive AD, wherein ZBP1 is activated by left-handed Z-DNA leaking from mitochondria, presenting new molecular targets for AD therapeutics.

Publication types

  • Comment

MeSH terms

  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / metabolism
  • Animals
  • DNA-Binding Proteins* / metabolism
  • Humans
  • Inflammation / immunology
  • Mice
  • Microglia* / immunology
  • Microglia* / metabolism
  • Mitochondria / metabolism
  • RNA-Binding Proteins* / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases* / metabolism
  • Signal Transduction

Substances

  • DNA-Binding Proteins
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • RNA-Binding Proteins