构建α-突触核蛋白异构体诱导食蟹猴多系统萎缩模型及相关机制研究

α-synuclein（α-syn）阳性包涵体在神经系统形成及播散是α-突触核蛋白病共同病理特征。α-syn阳性包涵体选择性累及神经系统特定区域导致不同疾病症候群。多系统萎缩（MSA）是一种进展迅速、预后差的α-突触核蛋白病。以泌尿及性功能障碍为主的自主神经障碍是其主要临床表现。目前MSA动物模型均为神经毒物或转基因模型，仅展现MSA部分病理改变及运动症状。本项目前期研究发现：运动障碍出现前MSA患者膀胱已有α-syn阳性包涵体沉积。进一步构建α-syn阳性包涵体从膀胱肌层神经末梢沿泌尿生殖相关自主神经通路逆行播散至大脑的大鼠MSA模型，成功模拟MSA自主神经功能障碍及运动障碍。此结果提示：α-syn阳性包涵体沿泌尿生殖相关自主神经通路逆行播散可能导致MSA症候群。本项目拟构建国内外首例非毒物、非转基因、α-syn蛋白异构体诱导食蟹猴MSA模型，为探索灵长类MSA致病机制提供更好平台。

The common pathogenesis of α-synucleinopathies is formation and propagation of α-synuclein (α-syn) positive inclusions in central nervous system. α-Syn positive inclusions are not evenly distributed in central nervous system, but affect the certain type of cells and regions, and induce the different symptoms. Multiple system atrophy (MSA) is a kind of rapidly progressive α-synucleinopathies with poor prognosis. Autonomic dysfunctions, such as sexual dysfunction and uropoiesis dysfunction, are main symptoms of MSA. So far, animal models of MSA are mainly toxicant-induced model or transgenic animal model, and all of the models only displayed the movement dysfunction of MSA. Our previous study suggested that before the movement dysfunction onset, α-syn positive inclusions were detected in the bladders of MSA. Then we established an SD rat model, which α-syn positive inclusions spreaded from genitourinary autonomic pathways to brain, and induced the symptoms of MSA. In this research project, we plan to established the first non-toxic,non-transgenic, α-syn strains induced cynomolgus macaque model for MSA. We will try to establishes a batter platform for study the pathogenesis of MSA in primate.