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• W4307777491 abstract "Stimulator of interferon genes (STING) is activated after detection of cytoplasmic dsDNA by cGAS (cyclic GMP-AMP synthase) as part of the innate immunity defence against viral pathogens. STING binds TANK-binding kinase 1 (TBK1). TBK1 mutations are associated with familial amyotrophic lateral sclerosis, and the STING pathway has been implicated in the pathogenesis of further neurodegenerative diseases. To test whether STING activation is sufficient to induce neurodegeneration, we analysed a mouse model that expresses the constitutively active STING variant N153S. In this model, we focused on dopaminergic neurons, which are particularly sensitive to stress and represent a circumscribed population that can be precisely quantified. In adult mice expressing N153S STING, the number of dopaminergic neurons was smaller than in controls, as was the density of dopaminergic axon terminals and the concentration of dopamine in the striatum. We also observed alpha-synuclein pathology and a lower density of synaptic puncta. Neuroinflammation was quantified by staining astroglia and microglia, by measuring mRNAs, proteins and nuclear translocation of transcription factors. These neuroinflammatory markers were already elevated in juvenile mice although at this age the number of dopaminergic neurons was still unaffected, thus preceding the degeneration of dopaminergic neurons. More neuroinflammatory markers were blunted in mice deficient for inflammasomes than in mice deficient for signalling by type I interferons. Neurodegeneration, however, was blunted in both mice. Collectively, these findings demonstrate that chronic activation of the STING pathway is sufficient to cause degeneration of dopaminergic neurons. Targeting the STING pathway could therefore be beneficial in Parkinson's disease and further neurodegenerative diseases.Neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases are characterised by neurons getting damaged and dying. Many factors contribute to this process, but few can be effectively controlled by therapies. Interestingly, previous studies have highlighted that inflammation, a process normally triggered by foreign agents or biological damage, is often associated with neurons degenerating. However, it is unclear whether these responses are the cause or the consequence of brain cell damage. In injured neurons, the genetic information normally contained inside a dedicated cellular compartment can start to leak into the surrounding parts of the cell. This damage triggers an inflammatory response through the STING pathway, a mechanism previously implicated in the onset of Parkinson’s disease. In these patients, the neurons that produce the signalling molecule dopamine start to die, leading to difficulty with movement. Whether STING can directly cause this neuronal loss remains unknown. To answer this question, Szegö, Malz et al. genetically engineered mice in which the STING pathway is permanently activated. The animals had fewer dopamine-producing neurons and accumulated harmful clumps of proteins; both these biological features are characteristic signs of Parkinson’s disease. Crucially, signs of inflammation were present before neurons started to show damage, suggesting that inflammatory responses could cause neurodegeneration. Further experiments revealed that STING triggers several molecular cascades; blocking one only of these pathways did not keep the neurons healthy. Neurodegenerative diseases are a growing concern around the world. The results from Szegö, Malz et al. suggest that preventing prolonged inflammatory may reduce the risk of neurodegeneration. If further research confirms these findings, in particular in humans, well-known treatments against inflammation could potentially become relevant to fight these conditions." @default.
• W4307777491 created "2022-11-05" @default.
• W4307777491 creator A5038976396 @default.
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• W4307777491 date "2022-10-31" @default.
• W4307777491 modified "2023-10-18" @default.
• W4307777491 title "Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice" @default.
• W4307777491 cites W1496790952 @default.
• W4307777491 cites W1768846296 @default.
• W4307777491 cites W1868478050 @default.
• W4307777491 cites W1904705252 @default.
• W4307777491 cites W1923330562 @default.
• W4307777491 cites W1971840849 @default.
• W4307777491 cites W2015310325 @default.
• W4307777491 cites W2030851291 @default.
• W4307777491 cites W2031907924 @default.
• W4307777491 cites W2034369386 @default.
• W4307777491 cites W2035232303 @default.
• W4307777491 cites W2057358353 @default.
• W4307777491 cites W2072510538 @default.
• W4307777491 cites W2073118251 @default.
• W4307777491 cites W2089578389 @default.
• W4307777491 cites W2092288031 @default.
• W4307777491 cites W2098462847 @default.
• W4307777491 cites W2101167927 @default.
• W4307777491 cites W2108865709 @default.
• W4307777491 cites W2118403357 @default.
• W4307777491 cites W2131256783 @default.
• W4307777491 cites W2144259303 @default.
• W4307777491 cites W2156054547 @default.
• W4307777491 cites W2168126136 @default.
• W4307777491 cites W2236786161 @default.
• W4307777491 cites W2336534940 @default.
• W4307777491 cites W2431987552 @default.
• W4307777491 cites W2522054472 @default.
• W4307777491 cites W2559769595 @default.
• W4307777491 cites W2559922559 @default.
• W4307777491 cites W2560541542 @default.
• W4307777491 cites W2605759022 @default.
• W4307777491 cites W2622807556 @default.
• W4307777491 cites W2745809236 @default.
• W4307777491 cites W2758637781 @default.
• W4307777491 cites W2761784274 @default.
• W4307777491 cites W2765298868 @default.
• W4307777491 cites W2789323443 @default.
• W4307777491 cites W2795875233 @default.
• W4307777491 cites W2809089210 @default.
• W4307777491 cites W2887997888 @default.
• W4307777491 cites W2888969152 @default.
• W4307777491 cites W2888993058 @default.
• W4307777491 cites W2890670389 @default.
• W4307777491 cites W2901737658 @default.
• W4307777491 cites W2908658437 @default.
• W4307777491 cites W2913960606 @default.
• W4307777491 cites W2917383181 @default.
• W4307777491 cites W2924757324 @default.
• W4307777491 cites W2941630117 @default.
• W4307777491 cites W2941857520 @default.
• W4307777491 cites W2947550142 @default.
• W4307777491 cites W2953454103 @default.
• W4307777491 cites W2966261467 @default.
• W4307777491 cites W2973915710 @default.
• W4307777491 cites W2981342477 @default.
• W4307777491 cites W3007798226 @default.
• W4307777491 cites W3010750792 @default.
• W4307777491 cites W3014631621 @default.
• W4307777491 cites W3020906235 @default.
• W4307777491 cites W3024191006 @default.
• W4307777491 cites W3030848819 @default.
• W4307777491 cites W3087170892 @default.
• W4307777491 cites W3087818404 @default.
• W4307777491 cites W3090881569 @default.
• W4307777491 cites W3092551839 @default.
• W4307777491 cites W3099463467 @default.
• W4307777491 cites W3100860354 @default.
• W4307777491 cites W3107395714 @default.
• W4307777491 cites W3109605806 @default.
• W4307777491 cites W3136029617 @default.
• W4307777491 cites W3145334405 @default.
• W4307777491 cites W3151167688 @default.
• W4307777491 cites W3177516403 @default.
• W4307777491 cites W3180940268 @default.
• W4307777491 cites W3197824464 @default.
• W4307777491 cites W3202393461 @default.
• W4307777491 cites W3208415654 @default.
• W4307777491 cites W4211217520 @default.
• W4307777491 cites W4223521725 @default.
• W4307777491 cites W4223610665 @default.
• W4307777491 cites W4225916403 @default.
• W4307777491 cites W4239066152 @default.
• W4307777491 cites W4254075371 @default.
• W4307777491 doi "https://doi.org/10.7554/elife.81943" @default.
• W4307777491 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36314770" @default.
• W4307777491 hasPublicationYear "2022" @default.
• W4307777491 type Work @default.
• W4307777491 citedByCount "10" @default.

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