Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 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.

Language: Английский

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The mitophagy pathway and its implications in human diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 16, 2023

Abstract Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, crucial for metabolism survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria maintain mitochondrial fine-tuning numbers balance intracellular homeostasis. Growing evidences show that mitophagy, an acute tissue stress response, plays important role maintaining the health of network. Since timely removal abnormal is essential survival, cells have evolved variety mitophagy pathways ensure can be activated time under various environments. A better understanding diseases treatment therapeutic target design. In this review, we summarize molecular mechanisms mitophagy-mediated elimination, how maintains homeostasis at system levels organ, what alterations related development diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., recent advances. Finally, potential clinical applications outline conditions regulators enter trials. Research advances signaling transduction will developing new strategies precision medicine.

Language: Английский

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Cellular functions of cGAS-STING signaling

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 33(8), P. 630 - 648

Published: Nov. 24, 2022

Language: Английский

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Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer’s disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101503 - 101503

Published: Oct. 29, 2021

Language: Английский

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Role of the cGAS–STING pathway in systemic and organ-specific diseases

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 558 - 572

Published: June 22, 2022

Language: Английский

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Aging, Cellular Senescence, and Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(4), P. 1989 - 1989

Published: Feb. 11, 2022

Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts >95% of (AD) cases. The mechanism underlying aging-related susceptibility to LOAD unknown. Cellular senescence, a state permanent cell growth arrest, believed contribute importantly aging and diseases, including AD. Senescent astrocytes, microglia, endothelial cells, neurons have been detected in brain AD patients animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide tau-protein-induced neuropathologies, improves memory model mice, suggesting pivotal role cellular senescence pathophysiology. Nonetheless, although accumulated evidence supports AD, mechanisms that promote how neuropathophysiology remain largely This review summarizes recent advances this field. We believe removal represents promising approach toward effective treatment such as

Language: Английский

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Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Oct. 4, 2022

Abstract Stimulator of interferons genes (STING), which is crucial for the secretion type I and proinflammatory cytokines in response to cytosolic nucleic acids, plays a key role innate immune system. Studies have revealed participation STING pathway unregulated inflammatory processes, traumatic brain injury (TBI), spinal cord (SCI), subarachnoid haemorrhage (SAH) hypoxic–ischaemic encephalopathy (HIE). signalling markedly increased CNS injury, agonists might facilitate pathogenesis injury. However, effects STING-regulated activation are not well understood. Aberrant increases events, interferon responses, cell death. cGAS primary that induces activation. Herein, we provide comprehensive review latest findings related cGAS–STING highlight control mechanisms their functions Furthermore, summarize explore most recent advances toward obtaining an understanding involvement programmed death (autophagy, necroptosis, ferroptosis pyroptosis) during We also potential therapeutic agents capable regulating pathway, facilitates our value this as treatment target.

Language: Английский

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STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(15)

Published: April 8, 2022

In idiopathic Parkinson’s disease (PD), pathologic αSyn aggregates drive oxidative and nitrative stress that may cause genomic mitochondrial DNA damage. These events are associated with activation of the cyclic GMP-AMP synthase (cGAS)/stimulator interferon genes (STING) immune pathway, but it is not known whether STING activated in or contributes to α-synucleinopathies. Herein, we used primary cell cultures intrastriatal preformed fibril (αSyn-PFF) mouse model PD demonstrate pathology causes STING-dependent neuroinflammation dopaminergic neurodegeneration. microglia-astrocyte cultures, αSyn-PFFs induced double-strand break (DSB) damage response signaling (γH2A.X), as well TBK1 was blocked by inhibition. αSyn-PFF model, similarly observed increased γH2A.X within striatal microglia prior onset Using STING-deficient (Stinggt) mice, demonstrated α-Syn PFF STING-dependent. Furthermore, Stinggt mice were protected from PFF-induced motor deficits, accumulation, neuron loss. We also upregulation protein substantia nigra pars compacta (SNpc) human patients correlated significantly accumulation. upregulated treated αSyn-PFFs, which primed pathway mount stronger responses when exposed a agonist. Our results suggest microglial both neurodegeneration arising α-synucleinopathies, including PD.

Language: Английский

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Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice

Nature Aging, Journal Year: 2023, Volume and Issue: 3(2), P. 202 - 212

Published: Jan. 9, 2023

Language: Английский

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Neurogenesis in aging and age-related neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 78, P. 101636 - 101636

Published: April 29, 2022

Language: Английский

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