From Protector to Perpetrator: The cGAS-STING Pathway at the Intersection of Neurodegeneration and Neuroinflammation

Ghaleb Oriquat; Abdulqader Faris Abdulqader; Hamrayev Farid; Zarifjon Ashurov; Abduvali Sottarov; Nghm Yhya Ghafl; Neeraj Bainsal; Ritesh Singh

doi:10.1016/j.brainresbull.2026.111963

May 1, 2026Brain Research BulletinOpen Access

From Protector to Perpetrator: The cGAS-STING Pathway at the Intersection of Neurodegeneration and Neuroinflammation

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Key Points

This research aims to explore how the cGAS-STING pathway influences neuroinflammation and neurodegeneration in various neurological diseases.
Analyzed the role of cGAS-STING in CNS inflammation and neurodegeneration.
Investigated microglial activation and synapse pruning in models of ALS, FTD, Alzheimer's, Parkinson's, and Huntington's disease.
Proposed therapeutic strategies targeting cGAS-STING and biomarkers for effective CNS delivery.
cGAS-STING was found to trigger pathological synapse pruning and neurotoxic astrocyte conversion.
The pathway was activated by various forms of DNA, including nuclear and mitochondrial, in the aging and diseased brain.
Effective therapies must consider CNS delivery and combination with DNA-reducing strategies.

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Implication

Examines cGAS-STING involvement in neurodegeneration, suggesting it may drive neuroinflammation.

Abstract

• cGAS-STING switches from antiviral guardian to driver of sterile neuroinflammation in the CNS. • Microglial STING activation triggers pathological synapse pruning and neurotoxic astrocyte conversion. • Endogenous nuclear, mitochondrial, and retrotransposon DNA hijack cGAS-STING in aging and diseased brain. • cGAS-STING acts as a common inflammatory amplifier in ALS/FTD, Alzheimer's, Parkinson's, and Huntington's. • Effective therapy needs CNS delivery, biomarkers, and combination with upstream DNA-reducing strategies.

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Cite This Study

Oriquat et al. (2026) studied this question.

synapsesocial.com/papers/6a17da9b3fad632b0f9d7a1e https://doi.org/10.1016/j.brainresbull.2026.111963

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From Protector to Perpetrator: The cGAS-STING Pathway at the Intersection of Neurodegeneration and Neuroinflammation

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

From Protector to Perpetrator: The cGAS-STING Pathway at the Intersection of Neurodegeneration and Neuroinflammation

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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