Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Язык: Английский

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cGAS–STING drives ageing-related inflammation and neurodegeneration

Nature, Год журнала: 2023, Номер 620(7973), С. 374 - 380

Опубликована: Авг. 2, 2023

Low-grade inflammation is a hallmark of old age and central driver ageing-associated impairment disease1. Multiple factors can contribute to inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling their impact in natural ageing remain unclear. Here we show cGAS-STING pathway, which mediates immune sensing DNA3, critical chronic functional decline during ageing. Blockade STING suppresses phenotypes senescent human cells tissues, attenuates ageing-related multiple peripheral organs brain mice, leads an improvement tissue function. Focusing on brain, reveal activation triggers reactive microglial transcriptional states, neurodegeneration cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity microglia, defining mechanism by engaged brain. Single-nucleus RNA-sequencing analysis microglia hippocampi gain-of-function mouse model demonstrates engagement sufficient direct states leading bystander cell inflammation, neurotoxicity impaired memory capacity. Our findings establish pathway as blockade potential strategy halt neurodegenerative processes age.

Язык: Английский

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Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson’s disease

Neuron, Год журнала: 2022, Номер 110(15), С. 2422 - 2437.e9

Опубликована: Июнь 1, 2022

Язык: Английский

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Th17 cells and inflammation in neurological disorders: Possible mechanisms of action

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 22, 2022

Neurological disorders (NDs) are one of the leading causes global death. A sustained neuroinflammatory response has been reported to be associated with pathogenesis multiple NDs, including Parkinson’s disease (PD), sclerosis (MS), Alzheimer’s (AD), amyotrophic lateral (ALS), and major depressive disorder (MDD). Accumulating evidence shows that recruitment abundant lymphocytes in central nervous system may contribute promoting development progress inflammation neurological disorders. As subset T lymphocytes, CD4 + cells have a critical impact on helper (Th) 17 is most studied Th subpopulations produces cytokines (e.g., IL-17A, IL-23, IL-21, IL-6, IFN-γ), abnormal excessive activation microglia other immune cell types. All these factors involved several However, possible mechanisms Th17 their immunopathology abovementioned not clarified completely. This review will summarize by which encephalitogenic inflammatory related strongly chronic neuroinflammation, thus perpetuating neurodegenerative processes NDs. Finally, potential therapeutic prospects NDs also discussed.

Язык: Английский

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STING trafficking as a new dimension of immune signaling

The Journal of Experimental Medicine, Год журнала: 2023, Номер 220(3)

Опубликована: Янв. 13, 2023

The cGAS-STING pathway is an evolutionarily conserved immune signaling critical for microbial defense. Unlike other innate pathways that largely rely on stationary cascades of events, STING highly mobile in the cell. activated ER, but only signals after it arrives Golgi, and then quickly degraded by lysosome. Each step trafficking through secretory regulated host factors. Homeostatic via COPI-, COPII-, clathrin-coated vesicles important maintaining baseline tissue cellular immunity. Aberrant vesicular or lysosomal dysfunction produces signal STING, which often leads to pathology mice humans. Many trafficking-mediated diseases appear impact central nervous system, leading neurodegeneration. Therefore, introduces a new dimension likely has broad implications human disease.

Язык: Английский

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Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Ноя. 8, 2023

Abstract DNA sensing is a pivotal component of the innate immune system that responsible for detecting mislocalized and triggering downstream inflammatory pathways. Among sensors, cyclic GMP-AMP synthase (cGAS) primary player in cytosolic DNA, including foreign from pathogens self-DNA released during cellular damage, culminating type I interferon (IFN-I) response through stimulator genes (STING) activation. IFN-I cytokines are essential mediating neuroinflammation, which widely observed CNS injury, neurodegeneration, aging, suggesting an upstream role cGAS pathway. In this review, we summarize latest developments on cGAS-STING DNA-driven various neurological diseases conditions. Our review covers current understanding molecular mechanisms activation highlights signaling cell types central peripheral nervous systems, such as resident brain cells, neurons, glial cells. We then discuss different neurodegenerative conditions, tauopathies, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, well aging senescence. Finally, lay out advancements research development inhibitors assess prospects targeting STING therapeutic strategies wide spectrum diseases.

Язык: Английский

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Inflammasome assembly in neurodegenerative diseases

Trends in Neurosciences, Год журнала: 2023, Номер 46(10), С. 814 - 831

Опубликована: Авг. 24, 2023

Язык: Английский

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Innate immune activation in neurodegenerative diseases

Immunity, Год журнала: 2024, Номер 57(4), С. 790 - 814

Опубликована: Апрель 1, 2024

Язык: Английский

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Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review)

International Journal of Molecular Medicine, Год журнала: 2024, Номер 53(5)

Опубликована: Апрель 2, 2024

Chronic neuroinflammation serves a key role in the onset and progression of neurodegenerative disorders. Mitochondria serve as central regulators neuroinflammation. In addition to providing energy cells, mitochondria also participate immunoinflammatory response disorders including Alzheimer's disease, Parkinson's multiple sclerosis epilepsy, by regulating processes such cell death inflammasome activation. Under inflammatory conditions, mitochondrial oxidative stress, epigenetics, dynamics calcium homeostasis imbalance may underlying regulatory mechanisms for these diseases. Therefore, investigating related dysfunction result therapeutic strategies against chronic neurodegeneration. The present review summarizes neuroinflammatory diseases current treatment approaches that target

Язык: Английский

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3327 - 3361

Опубликована: Май 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Язык: Английский

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