Jo Seong-Lae, Hong Eui-Ju
College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Antioxidants (Basel). 2024 Feb 13;13(2):230. doi: 10.3390/antiox13020230.
Alzheimer's disease (AD) is the leading cause of dementia and is one of the neurodegenerative diseases that are caused by neuronal death due to various triggers. Neuroinflammation plays a critical role in the development of AD. The neuroinflammatory response is manifested by pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; various chemokines; nitrous oxide; and reactive oxygen species. In this study, we evaluated the relevance of progesterone receptor membrane component 1 (PGRMC1), which is expressed in the brain cells during the induction of neuroinflammation. A lipopolysaccharide (LPS)-induced chronic neuroinflammation model and knockdown cells were used to assess the inflammatory cytokine levels, AD-related factors, inflammation-related signaling, and cell death. knockout (KO) mice had higher IL-1β levels after treatment with LPS compared with those of wild-type (WT) mice. Furthermore, KO mice had higher levels of inflammatory factors, endoplasmic reticulum stress indicators, and AD-associated markers compared with those of WT mice who underwent LPS treatment or not. Finally, these indicators were observed in vitro using U373-MG astrocytes. In conclusion, the loss of PGRMC1 may promote neuroinflammation and lead to AD.
阿尔茨海默病（AD）是痴呆的主要病因，是由各种触发因素导致神经元死亡所引起的神经退行性疾病之一。神经炎症在AD的发展过程中起关键作用。神经炎症反应表现为促炎细胞因子，如白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α；各种趋化因子；一氧化氮；以及活性氧。在本研究中，我们评估了孕酮受体膜成分1（PGRMC1）的相关性，其在神经炎症诱导过程中在脑细胞中表达。使用脂多糖（LPS）诱导的慢性神经炎症模型和基因敲低细胞来评估炎性细胞因子水平、AD相关因子、炎症相关信号传导和细胞死亡。与野生型（WT）小鼠相比，基因敲除（KO）小鼠在用LPS治疗后IL-1β水平更高。此外，与接受或未接受LPS治疗的WT小鼠相比，KO小鼠的炎症因子、内质网应激指标和AD相关标志物水平更高。最后，在体外使用U373-MG星形胶质细胞观察到了这些指标。总之，PGRMC1的缺失可能会促进神经炎症并导致AD。
