Yang Ying-Ying, Ren Yan-Tao, Jia Meng-Yu, Bai Chen-Yang, Liang Xiu-Ting, Gao Hui-Ling, Zhong Man-Li, Wang Tao, Guo Chuang
Institute of Neuroscience, College of Life and Health Sciences, Northeastern University, Shenyang 110169, China; Liaoning Cheng Da Biotechnology Co., Ltd, Shenyang 110179, China.
Institute of Neuroscience, College of Life and Health Sciences, Northeastern University, Shenyang 110169, China.
Exp Neurol. 2023 Apr;362:114346. doi: 10.1016/j.expneurol.2023.114346. Epub 2023 Feb 5.
Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) accumulates in the brains of Alzheimer's disease (AD) patients and may interact with Aβ or microtubule associated protein tau to associate with the neurodegenerative process. Increasing evidence indicates a potential protective effect of h-IAPP against Aβ-induced neurotoxicity in AD mouse models. However, a direct therapeutic effect of h-IAPP supplementation on tauopathy has not been established. Here, we found that long-term h-IAPP treatment attenuated tau hyperphosphorylation levels and induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration in the hippocampus, and alleviated behavioral deficits in P301S transgenic mice (a mouse model of tauopathy). Restoration of insulin sensitization, glucose/energy metabolism, and activated BDNF signaling also contributed to the underlying mechanisms. These findings suggest that seemly h-IAPP has promise for the treatment of neurodegenerative disorders with tauopathy, such as AD.
最近的证据表明，人胰岛淀粉样多肽（h-IAPP）在阿尔茨海默病（AD）患者的大脑中积累，并且可能与β淀粉样蛋白（Aβ）或微管相关蛋白tau相互作用，从而与神经退行性过程相关联。越来越多的证据表明，h-IAPP在AD小鼠模型中对Aβ诱导的神经毒性具有潜在的保护作用。然而，补充h-IAPP对tau蛋白病的直接治疗效果尚未得到证实。在此，我们发现长期h-IAPP治疗可降低tau蛋白的过度磷酸化水平，诱导神经炎症和氧化损伤，预防海马体中的突触丢失和神经元变性，并减轻P301S转基因小鼠（tau蛋白病小鼠模型）的行为缺陷。胰岛素敏感性、葡萄糖/能量代谢的恢复以及脑源性神经营养因子（BDNF）信号通路的激活也有助于其潜在机制。这些发现表明，看似h-IAPP有望用于治疗tau蛋白病相关的神经退行性疾病，如AD。
