Donald W. Reynolds Department of Geriatrics and Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2023 Jan 4;24(2):950. doi: 10.3390/ijms24020950.
a key pathogen in periodontitis, is associated with neuroinflammation. Periodontal disease increases with age; 70.1% of adults 65 years and older have periodontal problems. However, the - lipopolysaccharide (LPS)induced mitochondrial dysfunction in neurodegenerative diseases remains elusive. In this study, we investigated the possible role of -LPS in mitochondrial dysfunction during neurodegeneration. We found that -LPS treatment activated toll-like receptor (TLR) 4 signaling and upregulated the expression of Alzheimer's disease-related dementia and neuroinflammatory markers. Furthermore, the LPS treatment significantly exacerbated the production of reactive oxygen species and reduced the mitochondrial membrane potential. Our study highlighted the pivotal role of -LPS in the repression of serum response factor (SRF) and its co-factor p49/STRAP that regulate the actin cytoskeleton. The LPS treatment repressed the genes involved in mitochondrial function and biogenesis. -LPS negatively altered oxidative phosphorylation and glycolysis and reduced total adenosine triphosphate (ATP) production. Additionally, it specifically altered the mitochondrial functions in complexes I, II, and IV of the mitochondrial electron transport chain. Thus, it is conceivable that -LPS causes mitochondrial dysfunction through oxidative stress and inflammatory events in neurodegenerative diseases.
牙龈卟啉单胞菌是牙周炎的主要病原体，与神经炎症有关。牙周病随着年龄的增长而增加；70.1%的 65 岁及以上成年人有牙周问题。然而，脂多糖（LPS）诱导的神经退行性疾病中的线粒体功能障碍仍然难以捉摸。在这项研究中，我们研究了 -LPS 在神经退行性变过程中线粒体功能障碍中的可能作用。我们发现，-LPS 处理激活了 Toll 样受体（TLR）4 信号通路，并上调了阿尔茨海默病相关痴呆和神经炎症标志物的表达。此外，LPS 处理显著加剧了活性氧的产生并降低了线粒体膜电位。我们的研究强调了 -LPS 在抑制血清反应因子（SRF）及其调节肌动蛋白细胞骨架的辅助因子 p49/STRAP 中的关键作用。LPS 处理抑制了参与线粒体功能和生物发生的基因。-LPS 负调控氧化磷酸化和糖酵解，并减少总三磷酸腺苷（ATP）的产生。此外，它还特异性地改变了线粒体电子传递链复合体 I、II 和 IV 中的线粒体功能。因此，可以想象，-LPS 通过神经退行性疾病中的氧化应激和炎症事件导致线粒体功能障碍。
