Evidence map›Paper›PMID 34459078›Full record

ArticleAging cell2021

Inhibition of the cGAS-STING pathway ameliorates the premature senescence hallmarks of Ataxia-Telangiectasia brain organoids.

Julio Aguado, Harman K Chaggar, Cecilia Gómez-Inclán, Mohammed R Shaker, Hannah C Leeson, Alan Mackay-Sim, Ernst J Wolvetang

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06324877 (Single Arm Open-label Clinical Trial in Ataxia-telangiectasia to Test the Effects of Nicotinamide Riboside on Ataxia Scales, Immune Function, and Neurofilament Light Chain.), which is not on this map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06324877 naunknown statusnot on this mapstarted 2024, after this paper: background citation

Single Arm Open-label Clinical Trial in Ataxia-telangiectasia to Test the Effects of Nicotinamide Riboside on Ataxia Scales, Immune Function, and Neurofilament Light Chain.

TypeinterventionalSponsorThe University of QueenslandRan2024 to 2025Enrolled10ConditionsAtaxia TelangiectasiaArmsNicotinamide riboside
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

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  13. A noncanonical cGAS-STING pathway drives cellular and organismal aging.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  14. Biomaterials science · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Julio AguadoAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.ORCID 0000-0002-1841-4741
Harman K ChaggarAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.
Cecilia Gómez-InclánAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.
Mohammed R ShakerAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.
Hannah C LeesonAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.
Alan Mackay-SimDepartment of Neurogenetics, Kolling Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Ernst J WolvetangAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Saint Lucia, Queensland, Australia.ORCID 0000-0002-2146-6614
The University of Queensland · AUGriffith University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ataxia-telangiectasia (A-T) is a genetic disorder caused by the lack of functional ATM kinase. A-T is characterized by chronic inflammation, neurodegeneration and premature ageing features that are associated with increased genome instability, nuclear shape alterations, micronuclei accumulation, neuronal defects and premature entry into cellular senescence. The causal relationship between the detrimental inflammatory signature and the neurological deficiencies of A-T remains elusive. Here, we utilize human pluripotent stem cell-derived cortical brain organoids to study A-T neuropathology. Mechanistically, we show that the cGAS-STING pathway is required for the recognition of micronuclei and induction of a senescence-associated secretory phenotype (SASP) in A-T olfactory neurosphere-derived cells and brain organoids. We further demonstrate that cGAS and STING inhibition effectively suppresses self-DNA-triggered SASP expression in A-T brain organoids, inhibits astrocyte senescence and neurodegeneration, and ameliorates A-T brain organoid neuropathology. Our study thus reveals that increased cGAS and STING activity is an important contributor to chronic inflammation and premature senescence in the central nervous system of A-T and constitutes a novel therapeutic target for treating neuropathology in A-T patients.

Indexed as

AspirinAstrocytesAtaxia TelangiectasiaBrainCells, CulturedCellular SenescenceCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDose-Response Relationship, DrugHumansMembrane ProteinsNucleotidyltransferasesOrganoidsSTING ProteinAspirincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteinAtaxia-Telangiectasiabrain agingbrain organoidscellular senescencecGAS-STING signallingneurodegeneration

Identifiers

PMID34459078
PMCPMC8441292
OpenAlexW3197038471

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.