The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults DOI Creative Commons

Per Arkenberg,

Manuela Dittmar

GeroScience, Journal Year: 2023, Volume and Issue: 46(2), P. 2489 - 2502

Published: Nov. 22, 2023

Abstract It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, particular inflammaging, that associated with increased levels of TNF-α. This study aimed (1) investigate 24-h profiles for change during and (2) analyze relationship TNF-α, central body fat, cortisol oxidative DNA/RNA damage. In a cross-sectional 20 older young women, salivary OGG1, damage were quantified by ELISAs every 4 h period. Trunk circumferences taken as measures fat. Older compared exhibited significantly lower protein throughout whole period, 2.5 times mean level ( P < 0.00001) loss variation OGG1. Both age groups demonstrated significant TNF-alpha, The TNF-α was more than twice high women = 0.011). Regression analysis detected age, waist circumference negative predictors explaining 56% variance 0.00001), while no Results indicate strong decrease natural cellular aging. relationship, found between circumference, suggests involvement proinflammatory processes repair.

Language: Английский

Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions DOI Creative Commons
Yujun Hou,

Xixia Chu,

Jae Hyeon Park

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 4212 - 4233

Published: May 16, 2024

Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects UA's long-term treatment AD mechanisms action are unknown.

Language: Английский

Citations

22
Oxidized mitochondrial DNA activates the cGAS-STING pathway in the neuronal intrinsic immune system after brain ischemia-reperfusion injury DOI Creative Commons

Qingsheng Li,

Lingfei Yang,

Kaixin Wang

et al.

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(4), P. e00368 - e00368

Published: April 30, 2024

In the context of stroke and revascularization therapy, brain ischemia-reperfusion injury is a significant challenge that leads to oxidative stress inflammation. Central cell's intrinsic immunity cGAS-STING pathway, which typically activated by unusual DNA structures. The involvement oxidized mitochondrial (ox-mtDNA)-an byproduct-in this type neurological damage has not been fully explored. This study among first examine effect ox-mtDNA on innate neurons following injury. Using rat model transient middle cerebral artery occlusion cellular oxygen-glucose deprivation/reoxygenation, we have discovered activates pathway in neurons. Importantly, pharmacologically limiting release into cytoplasm reduces inflammation improves functions. Our findings suggest targeting may be valuable strategy attenuate therapy for acute ischemic stroke.

Language: Английский

Citations

16
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Language: Английский

Citations

3
Mitochondrial DNA-activated cGAS-STING pathway in cancer: Mechanisms and therapeutic implications DOI

Lintao Xia,

Xiuli Yan, Hui Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1880(1), P. 189249 - 189249

Published: Dec. 17, 2024

Language: Английский

Citations

5
Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus DOI
Yogesh Mishra, Ashutosh Kumar, Ravinder K. Kaundal

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Language: Английский

Citations

4
New perspectives on DNA methylation modifications in ocular diseases DOI

Faliang Zong,

Deshui Jia, Gang Huang

et al.

International Journal of Ophthalmology, Journal Year: 2025, Volume and Issue: 18(2), P. 340 - 350

Published: Jan. 16, 2025

The methylation of DNA is a prevalent epigenetic modification that plays crucial role in the pathological progression ocular diseases. can regulate gene expression, thereby affecting cell function and signal transduction. Ophthalmic diseases are kind complex diseases, their pathogenesis involves many factors such as genetic, environmental individual differences. In addition, inflammation, oxidative stress lipid metabolism, which abnormal closely related to, also considered to be major eye current understanding becoming more comprehensive. addition simple suppression expression by hypermethylation, hypomethylation or demethylation, non-promoter regions, interactions with other modifications, dynamic changes must considered. Interestingly, although some genes at levels, not significantly changed, indirectly reflects complexity regulation. This review aims summarize compare relevant studies, provide new ideas methods for prevention treatment different glaucoma, retinoblastoma, diabetic retinopathy.

Language: Английский

Citations

0
Expression of Neuronal Nicotinic Acetylcholine Receptor and Early Oxidative DNA Damage in Aging Rat Brain—The Effects of Memantine DOI Open Access
Małgorzata Lewandowska, Agata Różycka, Teresa Grzelak

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1634 - 1634

Published: Feb. 14, 2025

Aging and age-related neurodegenerative disorders are characterized by the dysfunction or loss of brain nicotinic acetylcholine receptors (nAChRs), these changes may be related to other senescence markers, such as oxidative stress DNA repair dysfunction. However, mechanism nAChR in aging modification this process drugs (e.g., memantine, Mem) not yet fully understood. To study whether differences expression rat occur due modulated Mem, we analyzed subunits (at RNA protein levels) biomarkers real-time quantitative polymerase chain reaction (RQ-PCR) Western blot validation. Twenty-one female Wistar rats were divided into four groups, depending on age, oldest group received injections Mem water with use intragastric catheters. We studied cerebral grey matter (CGM), subcortical white (SCWM), cerebellum (Ce). Results showed an decrease α7 mRNA level SCWM. The was accompanied reduced 8-oxoguanine glycosylase 1 (OGG1) increased tumor necrosis factor alpha (TNFα) level. In group, observed a higher SCWM Ce. Biomarker levels changed, but different extent area. Importantly, antioxidative status stopped even regressed under treatment. After two weeks treatment, increase TP53 8-oxo-2'deoxyguanosine (8-oxo-2'dG) observed. conclude that administration protective against mechanisms.

Language: Английский

Citations

0
Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges. DOI Creative Commons
Xavier Renaudin, Anna Campalans

DNA repair, Journal Year: 2025, Volume and Issue: 149, P. 103827 - 103827

Published: March 16, 2025

Oxidative DNA damage, resulting from endogenous cellular processes and external sources plays a significant role in mutagenesis, cancer progression, the pathogenesis of neurological disorders. Base Excision Repair (BER) is involved repair base modifications such as oxidations or alkylations well single strand breaks. The glycosylase OGG1, initiates BER pathway by recognition excision 8oxoG, most common oxidative lesion, both nuclear mitochondrial DNA. Beyond repair, OGG1 modulates transcription, particularly pro-inflammatory genes, linking damage to broader biological like inflammation aging. In therapy, inhibition has emerged promising strategy enhance treatment efficacy. Targeting sensitizes cells chemotherapies, radiotherapies, PARP inhibitors, presenting opportunities overcome therapy resistance. Additionally, activators hold potential mitigating associated with aging This review presents development several inhibitors how they have contributed advance our knowledge fundamental functions OGG1. We also discuss new provide for clinical applications treating cancer, Finally, we highlight challenges targeting regarding off-target effects recently reported some can these limitations.

Language: Английский

Citations

0
DNA damage, obesity and obesity-related health complications: what are new data telling us? DOI
Marta Włodarczyk, Grażyna Nowicka

Current Opinion in Clinical Nutrition & Metabolic Care, Journal Year: 2024, Volume and Issue: 27(4), P. 325 - 330

Published: April 19, 2024

Obesity is associated with increased DNA damage, which may in turn contribute to the development of obesity-related complications. damage can also affect adipocyte biology, resulting adiposity. Carefully managed weight loss programs reverse this process. This article surveys new data that support these contentions.

Language: Английский

Citations

2
DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products DOI Creative Commons
Kathleen M. Urrutia,

Yu Hsuan Chen,

Jin Tang

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Abstract Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and maintained by repair, turnover, dynamics mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) a major mechanism in mammalian mitochondria. BER enzymes are implicated mtDNA-mediated immune response inflammation. mtDNA organized into nucleoids transcription factor A (TFAM). The regulation activities TFAM-DNA interactions remains understudied. Here, we demonstrate modulation TFAM concentrations, sequences modifications. Unlike previously reported inhibitory effects, observed that human uracil-DNA glycosylase 1 (UNG1) AP endonuclease I (APE1) have optimal at specific TFAM/DNA molar ratios. High ratios inhibited other enzymes, OGG1 AAG. In addition, reduces accumulation certain intermediates. Molecular simulations DNA-binding experiments presence 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) sequence motifs enhances binding, partially explaining inhibition activity. Bioinformatic analysis published 8-oxodG, dU, TFAM-footprint maps reveals correlation between 8-oxodG locations Collectively, these results highlight complex sequence, lesions enzymes.

Language: Английский

Citations

2