The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 4, 2025

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing damage-associated molecular patterns (DAMPs), inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation this pathway culminates in AD-related neuroinflammation neurodegeneration. A substantial body mitochondria are involved critical pathogenic mechanisms AD, whose damage leads release mitochondrial (mtDNA) into extramitochondrial space. This leaked mtDNA serves DAMP, various pattern recognition receptors defense networks brain, including cGAS-STING pathway, ultimately leading an imbalance homeostasis. Therefore, modulation mtDNA-cGAS-STING restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In review, we focus on during stress activation pathway. Additionally, delve research progress further discuss primary directions potential hurdles developing targeted therapeutic drugs, gain deeper understanding pathogenesis provide new approaches its therapy.

Language: Английский

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Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship

Journal of Neuroscience Research, Journal Year: 2024, Volume and Issue: 102(2)

Published: Feb. 1, 2024

Abstract Synapses serve as the points of communication between neurons, consisting primarily three components: presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through release reception neurotransmitters. Synaptic plasticity, ability synapses to undergo structural functional changes, is influenced by proteins such growth‐associated proteins, vesicle density neurotrophic growth factors. Furthermore, maintaining plasticity consumes more than half brain's energy, with a significant portion this energy originating from ATP generated mitochondrial metabolism. Consequently, quantity, distribution, transport, function mitochondria impact stability brain metabolism, thereby participating in regulation fundamental processes including neuronal differentiation, neurite outgrowth, synapse formation, neurotransmitter release. This article provides comprehensive overview associated common factors two, well relationship metabolism plasticity.

Language: Английский

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Low-intensity pulsed ultrasound enhances delivery of 30 nm Q10 for improving mental and memory disorder in APP/PS1 mice

Drug Delivery and Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Language: Английский

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The cGAS‐STING‐related signature affects the prognosis of colorectal cancer through its regulation of multiple immune cells

IUBMB Life, Journal Year: 2025, Volume and Issue: 77(3)

Published: March 1, 2025

The cGAS-STING signaling pathway has emerged as a critical player in the immune response against cancer, including colorectal adenocarcinoma (COAD). Understanding impact of this on COAD at multiple omics levels is crucial for advancing cancer immunotherapy and precision medicine. This study aimed to investigate relationship between cGAS-STING-related genes COAD, analyzing gene mutations, copy number variations, DNA methylation, expression uncover pathway's influence prognosis. Utilizing multi-omics sequencing data from TCGA GEO databases, key core were identified further validated through PCR Western blot analysis. Mutations variations CASP8 RIPK1 genes, differential methylation patterns, mRNA specific assessed determine their Validation tissue samples highlighted NLRC3, CASP1, AIM2, CXCL10 pathway. Our findings demonstrate that mutations RIPK1, altered significantly prognosis COAD. identification pathway, particularly CXCL10, led development prognostic model predicting poor tumor outcomes cell infiltration. provides valuable insights into mechanisms offers potential directions future research

Language: Английский

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Impact of Diet and Exercise on Mitochondrial Quality and Mitophagy in Alzheimer's disease

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102734 - 102734

Published: March 1, 2025

Language: Английский

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Study on the neuroprotective effect of Zhimu-Huangbo extract on mitochondrial dysfunction in HT22 cells induced by D-galactose by promoting mitochondrial autophagy

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 318, P. 117012 - 117012

Published: Aug. 10, 2023

Zhimu-Huangbo (ZB) herb pair is a common prescription drug used by physicians of all dynasties, and has significant neuroprotective effect, such as the ZB can significantly promote neuronal cell regeneration, repair damage, improve cognitive disorders. However, its ingredients are urgently needed to be identified mechanisms remained unclear. Using ultra performance liquid chromatography-quadrupole-time flight-mass spectrometry (UPLC-Q-TOF-MS), study mechanism extract (ZBE) investigated, network pharmacology technology experimental validation also performed. Firstly, UPLC-Q-TOF-MS was characterize chemical components contained in ZBE. After that, TCMSP database Swiss Target Prediction method were search for potential target genes ZBE compounds. At same time, OMIM GeneCards disease databases Alzheimer's (AD) targets expanded with GEO database. Then, GO KEGG enrichment analysis performed using OECloud tools. Subsequently, therapeutic AD predicted pharmacological experimentally studied verified vitro. In ZBE, total 39 compounds characterized including Neomangiferin, Oxyberberine, Timosaponin D, Berberine, A-III, Anemarsaponin E, A-I, Smilagenin so on. A 831 13995 AD-related screened. further revealed number between 698. Through analysis, we found that ZBE's anti-AD enriched autophagy mitochondrial related pathways. The results experiments confirmed induced D-galactose (D-gal) HT22 cells through PTEN-induced kinase 1/Parkin (PINK1/Parkin) pathway. mitochondria play protective role on damaged neurons.

Language: Английский

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Pathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 94(4), P. 1265 - 1301

Published: July 7, 2023

Alzheimer’s disease (AD), the most common cause of dementia, is a chronic neurodegenerative induced by multiple factors. The high incidence and aging global population make it growing health concern with huge implications for individuals society. clinical manifestations are progressive cognitive dysfunction lack behavioral ability, which not only seriously affect quality life elderly, but also bring heavy burden to family Unfortunately, almost all drugs targeting classical pathogenesis have achieved satisfactory effects in past two decades. Therefore, present review provides more novel ideas on complex pathophysiological mechanisms AD, including variety possible that been proposed recent years. It will be helpful find out key target effect pathway potential prevention treatment AD. In addition, animal models AD research outlined we examine their prospect future. Finally, Phase I, II, III, IV randomized trials or market were searched online databases (Drug Bank Online 5.0, U.S. National Library Medicine, Alzforum). this may provide useful information development new AD-based drugs.

Language: Английский

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Repurposing of Tibolone in Alzheimer’s Disease

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1115 - 1115

Published: July 13, 2023

Alzheimer’s disease (AD) is a debilitating neurodegenerative characterised by the accumulation of amyloid-beta and tau in brain, leading to progressive loss memory cognition. The causes its pathogenesis are still not fully understood, but some risk factors, such as age, genetics, hormones, may play crucial role. Studies show that postmenopausal women have higher developing AD, possibly due decrease hormone levels, especially oestrogen, which be directly related reduction activity oestrogen receptors, beta (ERβ), favours more hostile cellular environment, mitochondrial dysfunction, mainly affecting key processes transport, metabolism, oxidative phosphorylation. Given influence hormones on biological at level, therapies clinical interest reduce or delay onset symptoms associated with AD. One drug potential tibolone, used clinics treat menopause-related symptoms. It can amyloid burden benefits integrity dynamics. Many protective effects mediated through steroid receptors also neuroglobin, whose elevated levels been shown protect against neurological diseases. Its importance has increased exponentially implication In this review, we discuss recent advances focusing mitochondrial-protective effects, highlight how valuable compound could therapeutic alternative mitigate molecular pathways characteristic

Language: Английский

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Mapping trends and hotspots of mitochondrial dysfunction in Alzheimer’s disease from 2013 to 2022: a bibliometric analysis of global research

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 26, 2023

Alzheimer's disease (AD), a prevalent neurodegenerative affliction that predominantly affects the elderly population, imposes substantial burden on not only patients but also their families and society at large. Mitochondrial dysfunction plays an important role in its pathogenesis. In this study, we conducted bibliometric analysis of research mitochondrial AD over past 10 years, with aim summarizing current hotspots trends field.On February 12, 2023, searched for publications about Web Science Core Collection database from 2013 to 2022. VOSview software, CiteSpace, SCImago, RStudio were used analyze visualize countries, institutions, journals, keywords, references.The number rise until 2021 decreased slightly The United States ranks first publications, H-index, intensity international cooperation research. terms Texas Tech University has most publications. Journal Disease field research, while Oxidative Medicine Cellular Longevity have highest citations. is still direction Autophagy, autophagy, neuroinflammation are new hotspots. article Lin MT cited by analyzing references.Research gaining significant momentum as it provides crucial avenue treatment debilitating condition. This study sheds light present trajectory concerning molecular mechanisms underlying AD.

Language: Английский

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Targeting Mitophagy as a Potential Therapeutic Approach for Age‐Related Bone Diseases

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: 7(7)

Published: May 29, 2024

Abstract Accumulating evidence has suggested a strong correlation between age‐related bone diseases and abnormal metabolism of microenvironment‐related cells, including mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, osteocytes, chondrocytes. Mitochondrial dysfunction significantly impacts cell initiates the development progress numerous diseases. autophagy or mitophagy, process that selectively removes damaged dysfunctional mitochondria, is closely associated with maintaining mitochondrial quality control homeostasis. Recent studies indicate decisive regulatory role mitophagy in diseases, thereby pointing toward potential for manipulating levels as new treatment paradigm. Based on importance novelty present review offers an overview pathways involved meticulously examines its function Various methods targeting are also discussed, mainly biomaterials mitophagy‐modulatory capabilities, “old drugs bottle” (e.g., Metformin, Rapamycin), natural compounds, endogenous factors, cell‐based therapies. In conclusion, these innovative approaches uncover mitophagy‐related signals, pathways, mechanisms, may shed light mitophagy‐targeting treatments future.

Language: Английский

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