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α7-整合素表达降低与肌肉α-突触核蛋白在 MPTP 诱导的帕金森病小鼠模型中的关系。

Association between Decreased ITGA7 Levels and Increased Muscle α-Synuclein in an MPTP-Induced Mouse Model of Parkinson's Disease.

机构信息

Department of Meridian and Acupoint, College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea.

Research Institute of Korean Medicine, Sang Ji University, Wonju 26339, Korea.

出版信息

Int J Mol Sci. 2022 May 18;23(10):5646. doi: 10.3390/ijms23105646.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN), reducing dopaminergic levels in the striatum and affecting motor control. Herein, we investigated the potential relationship between integrin α7 () and α-synuclein (α-syn) in the muscle of methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice and C2C12 cells. To characterize the pathology of PD, we examined the expression of tyrosine hydroxylase (TH) in the SN of the midbrain. Compared with the control group, MPTP-treated mice showed a significant decrease in TH expression in the SN, accompanied by a significant decrease in muscle ITGA7 expression. Compared with the control group, α-syn expression was increased in the MPTP group. Furthermore, the pattern of α-syn expression in the MPTP group was similar to the ITGA7 expression pattern in the control group (linear forms). To determine the relationship between ITGA7 and PD, we examined the expression of ITGA7 and α-syn after knockdown using siRNA in C2C12 cells. ITGA7 expression significantly decreased while α-syn expression significantly increased in siRNA-treated C2C12 cells. These results suggest that decreased ITGA7 muscle expression could increase α-syn expression. Moreover, α-syn accumulation, induced by decreased muscle ITGA7, might contribute to PD pathology.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征是黑质(SN)中的多巴胺能神经元丧失,纹状体中的多巴胺水平降低,并影响运动控制。在此,我们研究了整合素α7()和α-突触核蛋白(α-syn)在甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的小鼠和 C2C12 细胞肌肉中的潜在关系。为了表征 PD 的病理学,我们检查了中脑 SN 中酪氨酸羟化酶(TH)的表达。与对照组相比,MPTP 处理组小鼠 SN 中的 TH 表达显著降低,同时肌肉 ITGA7 表达显著降低。与对照组相比,MPTP 组中α-syn 的表达增加。此外,MPTP 组中α-syn 的表达模式与对照组中 ITGA7 的表达模式相似(线性形式)。为了确定 ITGA7 与 PD 之间的关系,我们使用 siRNA 在 C2C12 细胞中检查了 ITGA7 和α-syn 的表达。siRNA 处理的 C2C12 细胞中 ITGA7 表达显著降低,而α-syn 表达显著增加。这些结果表明,肌肉中 ITGA7 的表达减少可能会增加α-syn 的表达。此外,由肌肉 ITGA7 减少引起的α-syn 积累可能导致 PD 病理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c397/9143933/f921a86f9ac5/ijms-23-05646-g001.jpg

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