College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Ecotoxicol Environ Saf. 2019 Mar;169:301-305. doi: 10.1016/j.ecoenv.2018.11.001. Epub 2018 Nov 17.
Epidemiological and toxicological studies have shown that ambient fine particulate matter (PM) is a healthy risk factor for neurodegenerative diseases. Hyperphosphorylated tau is the common feature of numerous neurodegenerative diseases known as tauopathy, which could be inhibited by insulin stimulation. However, the effects of PM on tau protein injury by disturbing the insulin signaling pathway still need to be illuminated. In present study, male C57BL/6 J mice were administered with PM to determine whether PM inhalation can induce tauopathy via the insulin resistance (IR) related pathway (IRS-1/AKT/GSK-3β signaling pathway). The results showed that PM treatment induced the generation of phosphorylated tau (P-tau) and contributed to the development of tauopathy because of the insulin signaling disorders in insulin targeting organs. As expected, the occurrence of central and peripheral IR and accompanying hyperinsulinemia aggravated the disturbance of the IRS-1/AKT/GSK-3β signaling pathway. These observations indicated that PM exposure led to neurodegenerative tau lesion, and insulin signaling pathway might be a potential therapeutic target for tauopathy.
流行病学和毒理学研究表明，环境细颗粒物（PM）是神经退行性疾病的健康危险因素。过度磷酸化的 tau 是被称为 tau 病的许多神经退行性疾病的共同特征，胰岛素刺激可以抑制 tau 病。然而，PM 通过干扰胰岛素信号通路对 tau 蛋白损伤的影响仍需要阐明。在本研究中，雄性 C57BL/6J 小鼠给予 PM，以确定 PM 吸入是否可以通过胰岛素抵抗（IR）相关途径（IRS-1/AKT/GSK-3β信号通路）诱导 tau 病。结果表明，PM 处理诱导磷酸化 tau（P-tau）的产生，并导致 tau 病的发生，因为胰岛素靶向器官中的胰岛素信号紊乱。正如预期的那样，中枢和外周 IR 的发生以及伴随的高胰岛素血症加重了 IRS-1/AKT/GSK-3β信号通路的紊乱。这些观察结果表明，PM 暴露导致神经退行性 tau 病变，胰岛素信号通路可能是 tau 病的潜在治疗靶点。
