The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases
Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understan...
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Elsevier
2024-11-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003115 |
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| author | Yuxin Zhang Meijuan Zou Hao Wu Jie Zhu Tao Jin |
| author_facet | Yuxin Zhang Meijuan Zou Hao Wu Jie Zhu Tao Jin |
| author_sort | Yuxin Zhang |
| collection | DOAJ |
| description | Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders. A critical challenge is the intricate interplay between neuroinflammation, neurodegeneration, and immune responses, which are not yet fully characterized. In recent years, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, a crucial immune response for intracellular DNA sensing, has gradually gained attention. However, the specific roles of this pathway within cellular types such as immune cells, glial and neuronal cells, and its contribution to ND pathogenesis, remain not fully elucidated. In this review, we systematically explore how the cGAS-STING signaling links various cell types with related cellular effector pathways under the context of NDs for multifaceted therapeutic directions. We emphasize the discovery of condition-dependent cellular heterogeneity in the cGAS-STING pathway, which is integral for understanding the diverse cellular responses and potential therapeutic targets. Additionally, we review the pathogenic role of cGAS-STING activation in Parkinson's disease, ataxia-telangiectasia, and amyotrophic lateral sclerosis. We focus on the complex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic strategies. |
| format | Article |
| id | doaj-art-9fa20b027af84044b9f95821e64b72c4 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-9fa20b027af84044b9f95821e64b72c42024-11-20T05:06:31ZengElsevierNeurobiology of Disease1095-953X2024-11-01202106710The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseasesYuxin Zhang0Meijuan Zou1Hao Wu2Jie Zhu3Tao Jin4Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, China; Department of Neurobiology, Care Sciences & Society, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, SwedenDepartment of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, China; Corresponding author at: Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 1#, 130021 Changchun, China.Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders. A critical challenge is the intricate interplay between neuroinflammation, neurodegeneration, and immune responses, which are not yet fully characterized. In recent years, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, a crucial immune response for intracellular DNA sensing, has gradually gained attention. However, the specific roles of this pathway within cellular types such as immune cells, glial and neuronal cells, and its contribution to ND pathogenesis, remain not fully elucidated. In this review, we systematically explore how the cGAS-STING signaling links various cell types with related cellular effector pathways under the context of NDs for multifaceted therapeutic directions. We emphasize the discovery of condition-dependent cellular heterogeneity in the cGAS-STING pathway, which is integral for understanding the diverse cellular responses and potential therapeutic targets. Additionally, we review the pathogenic role of cGAS-STING activation in Parkinson's disease, ataxia-telangiectasia, and amyotrophic lateral sclerosis. We focus on the complex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S0969996124003115cGAS-STINGMicrogliaAstrocyteNeuronInnate immune systemAdaptive immune system |
| spellingShingle | Yuxin Zhang Meijuan Zou Hao Wu Jie Zhu Tao Jin The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases Neurobiology of Disease cGAS-STING Microglia Astrocyte Neuron Innate immune system Adaptive immune system |
| title | The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| title_full | The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| title_fullStr | The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| title_full_unstemmed | The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| title_short | The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| title_sort | cgas sting pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases |
| topic | cGAS-STING Microglia Astrocyte Neuron Innate immune system Adaptive immune system |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003115 |
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