Scorpion Venom Heat-Resistant Synthetic Peptide Alleviates Neuronal Necroptosis in Alzheimer's Disease Model by Regulating Lnc Gm6410 Under PM(2.5) Exposure.

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(2.5)) 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(2.5) 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(2.5)-exacerbated AD progression and the mechanisms of SVHRSP in alleviating this process. Through the establishment of a PM(2.5) exposure model in AD mice and an in vitro model, it was found that PM(2.5) 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(2.5)-induced AD mice. WB, qRT-PCR, and other molecular biological assays indicate that Lnc Gm16410 regulates neuronal necroptosis under PM(2.5) exposure via the p38 MAPK pathway. SVHRSP is a potential regulator of AD progression by regulating Lnc Gm16410 to alleviate PM(2.5) exposure-induced necroptosis. These findings offer new insights into the mechanism through which PM(2.5) 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(2.5) exposure by investigating the mechanism of action of SVHRSP in alleviating AD.