Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 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.

Язык: Английский

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Advances in crosstalk among innate immune pathways activated by mitochondrial DNA

Heliyon, Год журнала: 2024, Номер 10(1), С. e24029 - e24029

Опубликована: Янв. 1, 2024

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling apoptosis. Recent studies have shown that mitochondria play an important role other pathophysiological functions addition to cellular energy metabolism. release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) activate Toll-like receptor 9 (TLR9), NOD-, LRR-, pyrin domain-containing 3 (NLRP3) inflammasome cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune pathways against foreign pathogenic microorganisms. The response promotes antimicrobial defense regulates antiviral signaling, their overactivation induces onset progression inflammatory diseases. In this paper, we review mtDNA activation crosstalk among activated by mtDNA, providing clues study diseases caused cytoplasmic translocation.

Язык: Английский

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Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(9)

Опубликована: Апрель 17, 2024

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes heavy economic burden on people and society. Although it well established IVDD associated with genetic susceptibility, ageing obesity, its pathogenesis remains incompletely understood. Previously, was thought to occur because of excessive mechanical loading leading destruction nucleus pulposus cells (NPCs), but studies have shown much more complex process inflammation, metabolic factors NPCs death can involve all parts the disc, characterized by causing extracellular matrix (ECM) degradation. The damage pattern like some programmed cell death, suggesting death. apoptosis pyroptosis been studied IVDD, intervertebral still not be fully elucidated using only traditional modalities. With increasing research, new modes PANoptosis, ferroptosis senescence found closely related degeneration. Among these, PANoptosis combines essential elements pyroptosis, necroptosis form highly coordinated dynamically balanced inflammatory process. Furthermore, we believe may also crosstalk senescence. Therefore, review progress research multiple deaths provide guidance for clinical treatment.

Язык: Английский

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Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 50, С. 274 - 294

Опубликована: Янв. 1, 2025

Язык: Английский

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RGD hydrogel-loaded ADSC extracellular vesicles mitigate uranium-induced renal injury via TLR4/NF-κB pathway inhibition

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 17, 2025

Uranium-induced kidney damage represents a major health concern due to its toxic effects, including mitochondrial dysfunction and inflammation. Mitochondrial DNA (mtDNA)-mediated pyroptosis is critical pathway in the pathogenesis of renal injury. The toll-like receptor 4 / nuclear factor-kappa B (TLR4/NF-κB) signaling plays pivotal role this process. Recent studies have shown that extracellular vesicles derived from adipose-derived stem cells (ADSCs-EVs) possess therapeutic potential their anti-inflammatory regenerative properties. Incorporating ADSCs-EVs into arginine-glycine-aspartate (RGD), hydrogels may enhance stability efficacy vivo. This study aims explore molecular mechanism by which RGD hydrogel-loaded modulate mtDNA-mediated suppressing TLR4/NF-κB alleviate uranium-induced Repairing was found mitigate mtDNA leakage, thereby inhibiting pyroptosis. alleviated cell pathway. In vivo animal experiments confirmed enhanced body improved against Our findings reveal effectively inhibit pathway, preventing alleviating damage. elucidation provides novel strategy for utilizing treating

Язык: Английский

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Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Июнь 1, 2024

As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged elderly are diagnosed with one or disorders such as osteoporosis (OP), osteoarthritis (OA), intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain reduced functionality. Chronic inflammation has been identified underlying cause various diseases, including DBJDs. Recently, excessive activation pyroptosis, a form programed cell death (PCD) mediated by inflammasomes, emerged primary driver harmful chronic inflammation. Consequently, pyroptosis potential target for preventing treating This review explored physiological pathological roles pathway in development its relation to Meanwhile, elaborated molecular mechanisms within individual types marrow joints, well interplay among different context Furthermore, this presented latest compelling evidence supporting idea regulating DBJDs treatment, discussed potential, limitations, challenges therapeutic strategies involving regulation. In summary, an interesting identity unregulated was proposed review, which undertaken spoiler peaceful coexistence between cells environment. Over extended course DBJDs, perpetuated activity through crosstalk cascades types, thus exacerbating inflammatory environment throughout entire Correspondingly, regulation therapy promising option clinical treatment

Язык: Английский

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Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies

Journal of Orthopaedic Translation, Год журнала: 2024, Номер 49, С. 181 - 206

Опубликована: Окт. 16, 2024

Язык: Английский

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Toll-Like Receptor 9 Aggravates Pulmonary Fibrosis by Promoting NLRP3-Mediated Pyroptosis of Alveolar Epithelial Cells

Inflammation, Год журнала: 2024, Номер 47(5), С. 1744 - 1761

Опубликована: Март 18, 2024

Язык: Английский

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NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 12, 2024

NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 leads to production pro-inflammatory cellular contents, such as interleukin (IL)-1β IL-18, induction inflammatory cell death known pyroptosis, thereby amplifying or sustaining inflammation. While balanced response beneficial for resolving damage promoting tissue healing, excessive activation pyroptosis can have harmful effects. The involvement has been observed various cardiovascular diseases (CVD). Indeed, its associated are closely linked key risk factors including hyperlipidemia, diabetes, hypertension, obesity, hyperhomocysteinemia. Exercise compared with medicine highly effective measure both preventing treating CVD. Interestingly, emerging evidence suggests exercise improves CVD inhibits activity pyroptosis. In this review, mechanisms pathogenic critically discussed. Importantly, purpose emphasize managing by suppressing proposes it foundation developing novel treatment strategies.

Язык: Английский

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Regulating pyroptosis by mesenchymal stem cells and extracellular vesicles: A promising strategy to alleviate intervertebral disc degeneration

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 116001 - 116001

Опубликована: Дек. 20, 2023

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate heavy burden on society. IVDD characterized by decrease in nucleus pulposus cells (NPCs) endogenous mesenchymal stem (MSCs), degradation the extracellular matrix, macrophage infiltration, blood vessel nerve ingrowth. To date, therapeutic approaches regarding mainly include conservative treatment surgical intervention. However, both only relieve symptoms rather than stop or revert progression IVDD, since pathogenesis not yet clear. Pyroptosis, Caspase family dependence conducted Gasdermin family, newly discovered mode programmed cell death. Pyroptosis has been observed NPCs, annulus fibrosus (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial neurons may contribute IVDD. MSCs are kind pluripotent that be found almost all tissues. have strong ability secrete vesicles (EVs), contain exosomes, microvesicles apoptotic bodies. EVs derived from play an important role pyroptosis regulation could beneficial for alleviating This review focuses clarifying improve MSCs.

Язык: Английский

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