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

Autophagy‐mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 29, 2024

Abstract Retinopathy of prematurity (ROP) is a retinal neovascularization (RNV) disease that characterized by abnormal blood vessel development in the retina. Importantly, etiology ROP remains understudied. We re‐analyzed previously published single‐cell data and discovered strong correlation between microglia RNV diseases, particularly ROP. Subsequently, we found reactive oxygen species reduced autophagy‐dependent protein degradation absent melanoma 2 (AIM2) hypoxic BV2 cells, leading to increased AIM2 accumulation. Furthermore, engineered knockout mice observed was significantly compared wild‐type mice. In vitro vascular function assays also demonstrated diminished angiogenic capabilities following knockdown cells. Mechanistically, enhanced M1‐type polarization via ASC/CASP1/IL‐1β pathway, resulting RNV. Notably, administration recombinant IL‐1β exacerbated angiogenesis, while its inhibition ameliorated condition. Taken together, our study provides novel therapeutic target for offers insight into interaction pyroptosis autophagy.

Language: Английский

The Role of the AIM2 Gene in Obesity-Related Glucose and Lipid Metabolic Disorders: A Recent Update

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2024, Volume and Issue: Volume 17, P. 3903 - 3916

Published: Oct. 1, 2024

Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, can recognize and bind to double stranded DNA (dsDNA), leading assembly of inflammasome. The inflammasome plays important proinflammation role many diseases, induce pyroptotic cell death. It has also been closely linked development progression metabolic diseases be activated obesity, diabetes, nonalcoholic fatty liver disease, atherosclerosis. In this article, we mainly review glucose metabolism, especially obesity-related disorders lipid provide insights better understand pathogenesis, clinical treatment disease.

Language: Английский