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

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

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The Inflammatory Mechanism of Parkinson’s Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut–Brain Axis

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 159 - 159

Published: Feb. 6, 2025

Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, precise etiology of remains elusive. This article explores inflammatory mechanisms linking gut microbiota disease, emphasizing alterations in and their metabolites that influence disease's progression through bidirectional transmission signals along gut-brain axis. Building on this mechanistic framework, further discusses research methodologies treatment strategies focused metabolites, including metabolomics detection techniques, animal model investigations, therapeutic approaches such dietary interventions, probiotic treatments, fecal transplantation. Ultimately, aims elucidate relationship between underlying thereby paving way for novel avenues condition.

Language: Английский

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Identification of Downregulated MECR Gene in Parkinson’s Disease Through Integrated Transcriptomic Analysis and Validation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 550 - 550

Published: Jan. 10, 2025

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein (α-syn) aggregation. Lipid metabolism dysfunction may contribute to PD progression. This study aims identify lipid metabolism-related genes (LMGs) associated with using an integrative transcriptomic analysis of microarray single-cell RNA sequencing (scRNA-seq) datasets from patients healthy controls. Differentially expressed (DEGs) related were identified, key further filtered weighted gene co-expression network (WGCNA) machine learning algorithms. Four LMGs, AGPAT2, ASAH2, FA2H, MECR being notably downregulated in both bulk analyses patients. downregulation was validated α-syn PFF-induced models. Virtual screening molecular simulations identified potential allosteric modulators MECR, which offer pathway for future therapeutic exploration. highlights as critical link between PD, suggesting the need investigation into its implications.

Language: Английский

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STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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STING: a multifaced player in cellular homeostasis

Human Molecular Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract The stimulator of interferon gene (STING) is an important innate immune mediator the cytoplasmic DNA sensing pathway. As a known for its role in response to infections, STING also surprisingly at center variety non-infectious human diseases, including cancer, autoimmune diseases and neurodegenerative diseases. Recent studies have shown that has many signaling activities, type I (IFN-I) other IFN-independent which are poorly understood. unique property being continuous transported from ER Golgi then lysosome. Mutations or trafficking cofactors associated with affecting multiple non-immune organs. Here, we review recent advances mechanisms based part on STING-associated monogenic inborn error

Language: Английский

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A good side of STING

Science Signaling, Journal Year: 2025, Volume and Issue: 18(884)

Published: April 29, 2025

The innate immunity mediator STING senses and repairs lysosomal dysfunction.

Language: Английский

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The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 202, P. 106710 - 106710

Published: Oct. 28, 2024

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by damage to specific cell populations in the nervous system, ultimately leading disability or death. Effective treatments for these still lacking, due limited understanding their pathogeneses, which involve multiple cellular and molecular pathways. The triggering an immune response is feature neurodegenerative disorders. A critical challenge intricate interplay between neuroinflammation, neurodegeneration, responses, not yet fully characterized. In recent years, cyclic GMP-AMP synthase (cGAS)-stimulator interferon gene (STING) pathway, crucial intracellular DNA sensing, has gradually gained attention. However, roles this pathway within types such as cells, glial neuronal its contribution ND pathogenesis, remain elucidated. review, we systematically explore how cGAS-STING signaling links various with related effector pathways under context NDs multifaceted therapeutic directions. We emphasize discovery condition-dependent heterogeneity integral diverse responses potential targets. Additionally, review pathogenic role activation Parkinson's disease, ataxia-telangiectasia, amyotrophic lateral sclerosis. focus on complex bidirectional Alzheimer's Huntington's sclerosis, revealing double-edged nature disease progression. objective elucidate pivotal pathogenesis catalyze new insights facilitating development novel strategies.

Language: Английский

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Advanced electrochemical detection methodologies for assessing neuroactive substance variability induced by environmental pollutants exposure

Environmental Technology & Innovation, Journal Year: 2024, Volume and Issue: unknown, P. 103965 - 103965

Published: Dec. 1, 2024

Language: Английский

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Nisin A elevates adenosine to achieve anti-inflammatory activity

Food & Function, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

This study uncovers that nisin A achieves excellent anti-inflammatory activity via enhancing the level of adenosine, followed by up-regulation sphingolipid signaling pathway and down-regulation purine metabolism.

Language: Английский

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