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Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson''s disease autonomic dysfunction 期刊论文

编号：

3A223764BBED74495D06B62811F2237A
作者：

Li, Yangxia#^[1]Tong, Qing(佟晴)#^[1]Wang, Ye#^[1]Cheng, Yue^[1];Geng, Yao^[1];Tian, Tian^[2];Yuan, Yongsheng(袁永胜)^[1]Fan, Yi*^[2]Lu, Ming(鲁明)*^[2]Zhang, Kezhong(张克忠)*^[1]
语种：

英文
期刊：

CELL DEATH DISCOVERY ISSN：2058-7716 2024 年 10 卷 1 期 ; JAN 26
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摘要：

Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson''s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated alpha-synuclein (p-alpha-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-alpha-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to alpha-synuclein preformed fibril (alpha-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-alpha-syn and TLR2. Furthermore, the role of TLR2 in p-alpha-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-alpha-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of alpha-syn PFF induced a time-dependent loss of viability, and p-alpha-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-alpha-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-alpha-syn/ TLR2 signaling pathway.
推荐引用方式
GB/T 7714：

Li Yangxia,Tong Qing,Wang Ye, et al. Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson''s disease autonomic dysfunction [J].CELL DEATH DISCOVERY,2024,10(1).
APA：

Li Yangxia,Tong Qing,Wang Ye,Cheng Yue,&Zhang Kezhong.(2024).Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson''s disease autonomic dysfunction .CELL DEATH DISCOVERY,10(1).
MLA：

Li Yangxia, et al. "Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson''s disease autonomic dysfunction" .CELL DEATH DISCOVERY 10,1(2024).
入库时间：

2/20/2024 5:23:35 AM
更新时间：

2/20/2024 5:23:35 AM
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