Qin Chuhao, Li Dongsheng, Zhang Jiahui, Yin Ze, Li Fasheng
College of Medical Laboratory, Dalian Medical University, Dalian 116044, China.
Int J Mol Sci. 2025 May 4;26(9):4372. doi: 10.3390/ijms26094372.
Recent epidemiological studies have indicated that exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less in the ambient air (PM) is significantly associated with an elevated risk of developing Alzheimer's disease (AD) and its progression. Scorpion venom heat-resistant synthetic peptide (SVHRSP) exhibits anti-inflammatory and neuroprotective properties. However, the exact ways in which SVHRSP mitigates the progression of AD induced by PM are still unknown. Long non-coding RNA (lncRNA) plays a crucial role in various biological processes. Necroptosis, a form of programmed cell death, has garnered considerable attention in recent years. This study aims to investigate whether Lnc Gm16410 and neuronal necroptosis are involved in PM-exacerbated AD progression and the mechanisms of SVHRSP in alleviating this process. Through the establishment of a PM exposure model in AD mice and an in vitro model, it was found that PM exposure could promote necroptosis and the down-regulation of Lnc Gm16410, thereby promoting the progression of AD. Behavioral tests showed that SVHRSP alleviated cognitive impairment in PM-induced AD mice. WB, qRT-PCR, and other molecular biological assays indicate that Lnc Gm16410 regulates neuronal necroptosis under PM exposure via the p38 MAPK pathway. SVHRSP is a potential regulator of AD progression by regulating Lnc Gm16410 to alleviate PM exposure-induced necroptosis. These findings offer new insights into the mechanism through which PM exposure accelerates the progression of AD, examined from the perspective of LncRNA. Furthermore, we offer new targets for the treatment and prevention of AD following PM exposure by investigating the mechanism of action of SVHRSP in alleviating AD.
近期的流行病学研究表明，暴露于环境空气中空气动力学直径为2.5μm或更小的颗粒物（PM）与患阿尔茨海默病（AD）及其病情进展风险升高显著相关。蝎毒耐热合成肽（SVHRSP）具有抗炎和神经保护特性。然而，SVHRSP减轻PM诱导的AD进展的确切方式仍不清楚。长链非编码RNA（lncRNA）在各种生物学过程中起关键作用。坏死性凋亡作为一种程序性细胞死亡形式，近年来受到了广泛关注。本研究旨在探讨Lnc Gm16410和神经元坏死性凋亡是否参与PM加重的AD进展以及SVHRSP缓解该过程的机制。通过在AD小鼠中建立PM暴露模型和体外模型，发现PM暴露可促进坏死性凋亡和Lnc Gm16410的下调，从而促进AD进展。行为测试表明，SVHRSP可减轻PM诱导的AD小鼠的认知障碍。蛋白质免疫印迹法（WB）、实时定量聚合酶链反应（qRT-PCR）及其他分子生物学检测表明，Lnc Gm16410在PM暴露下通过p38丝裂原活化蛋白激酶（MAPK）途径调节神经元坏死性凋亡。SVHRSP通过调节Lnc Gm16410减轻PM暴露诱导的坏死性凋亡，是AD进展的潜在调节因子。这些发现从lncRNA角度为PM暴露加速AD进展的机制提供了新见解。此外，通过研究SVHRSP缓解AD的作用机制，为PM暴露后AD的治疗和预防提供了新靶点。
