AdipoR1/PI3K/Akt信号通路介导运动延缓快眼动睡眠期行为障碍神经变性疾病进展的机制研究

α-突触核蛋白病（α-Syn病，帕金森病等）难以逆转，明确其保护因素及机制对防治意义重大。我们前期研究发现低运动量的特发性快眼动睡眠期行为障碍患者（iRBD，α-Syn病前驱期）更快进展为α-Syn病。预实验发现：运动是α-Syn病的保护因素；运动提高纹状体（α-Syn病核心部位）PI3K/Akt通路相关基因表达；而脂联素（运动可诱发其高表达）基因与α-Syn病显著关联。既往研究提示脂联素受体1(AdipoR1)/PI3K/Akt通路激活有神经保护作用。但运动延缓α-Syn病的机制不明。据此，我们提出“AdipoR1/PI3K/Akt通路介导运动延缓α-Syn病进展”的假说。本项目将通过iRBD队列研究、动物及细胞模型实验，阐明运动提高脂联素水平进而激活AdipoR1/PI3K/Akt通路延缓α-Syn病进展的作用机制。预期结果为延缓/阻断α-Syn病进展的干预措施开发提供理论和实验依据。

α-synucleinopathies (e.g., Parkinson's disease) are difficult to be reversed, and it is of great significance to clarify their protective factors and underlying mechanisms for their prevention and treatment. Our previous study found that patients with idiopathic REM sleep behavior disorder (iRBD, the prodromal stage of α-synucleinopathies prodromal phase) with lower exercise level progress to α-synucleinopathies faster. Our preliminary experiments suggested that 1) high exercise level is a protective factor of α-synucleinopathies; 2) exercise can increase the expression level of some proteins of the PI3K/Akt pathway; and 3) adiponectin gene variation is significantly associated with α-synucleinopathies. In addition, previous studies have found that exercise can significantly increase the level of adiponectin, and that the activation of the adiponectin receptor 1 (AdipoR1)/PI3K/Akt pathway has a protective effect on α-synucleinopathies. However, the underlying mechanisms of the protective effects of exercise on α-synucleinopathies progression remain unclear. Therefore, we hypothesize that "exercise increases adiponectin and subsequently activates the AdipoR1/PI3K/Akt signaling pathway to delay the progression of α-synucleinopathies". This project will employ iRBD cohort, animal and cellular model to clarify that the alleviation effect of exercise on α-synucleinopathies progression is mediated by the increased adiponectin level and its subsequent activation of the AdipoR1/PI3K/Akt signaling pathway. This project will clarify the pathogenesis of α-synucleinopathies and pave a way for the development of preventive and intervention strategies for α-synucleinopathies.