Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging

Research output: Contribution to journalReview articlepeer-review

Abstract

Recognition of foreign or misplaced nucleic acids is one of the principal modes by which the immune system detects pathogenic entities. When cytosolic DNA is sensed, a signal is relayed via the cGAS–STING pathway: this involves the activation of cyclic GMP-AMP (cGMP-AMP) synthase (cGAS) and generation of the cyclic dinucleotide cGAMP, followed by the induction of stimulator of interferon genes (STING). The cGAS–STING pathway responds to viral, bacterial, and self-DNA. Whereas it generally mediates immune surveillance and is often neuroprotective, excessive engagement of the system can be deleterious. This is relevant in aging and age-related neurological diseases, where neuroinflammation contributes to disease progression. This review focuses on cGAS–STING signaling in aging, neurodegeneration, and neuroinflammation, and on therapeutic implications.

Original languageEnglish (US)
Pages (from-to)83-96
Number of pages14
JournalTrends in neurosciences
Volume44
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • Huntington's disease
  • ataxia telangiectasia
  • cyclic GAMP
  • innate immune system
  • interferon-stimulated genes
  • senescence

ASJC Scopus subject areas

  • Neuroscience(all)

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