BACKGROUND Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, but is closely associated with damage to dopaminergic neurons. MSA progression is rapid. Hence, long-term drug treatments do not have any therapeutic benefits. We assessed the inhibitory effect of mesenchymal stem cells (MSCs) on double-toxin-induced dopaminergic neurodegenerative MSA. RESULTS Behavioral disorder was significantly improved and neurodegeneration was prevented following MSC transplantation. Proteomics revealed lower expression of polyamine modulating factor-binding protein 1 (PMFBP1) and higher expression of 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), but these changes were reversed after MSC transplantation. In the in vitro study, the 6-OHDA-induced effects were reversed following co-culture with MSC. However, PMFBP1 knockdown inhibited the recovery effect due to the MSCs. Furthermore, HMGCL expression was decreased following co-culture with MSCs, but treatment with recombinant HMGCL protein inhibited the recovery effects due to MSCs. CONCLUSIONS These data indicate that MSCs protected against neuronal loss in MSA by reducing polyamine- and cholesterol-induced neural damage.

中文翻译：

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使用人骨髓源性间充质干细胞通过减少多胺和胆固醇引起的神经损伤来预防多系统萎缩。

背景技术多系统萎缩症（MSA）是一种病因未知的偶发性神经退行性疾病，但与多巴胺能神经元的损害密切相关。MSA进展迅速。因此，长期药物治疗没有任何治疗益处。我们评估了间充质干细胞（MSCs）对双毒素诱导的多巴胺能神经变性MSA的抑制作用。结果MSC移植后行为障碍得到明显改善，神经变性得到了预防。蛋白质组学显示多胺调节因子结合蛋白1（PMFBP1）的较低表达和3-羟甲基-3-甲基戊二酰辅酶A裂解酶（HMGCL）的较高表达，但这些变化在MSC移植后被逆转。在体外研究中，与MSC共培养后，6-OHDA诱导的作用被逆转。然而，PMFBP1敲低抑制了由于MSC的恢复作用。此外，与MSC共培养后，HMGCL表达降低，但是用重组HMGCL蛋白处理抑制了由于MSC引起的恢复作用。结论这些数据表明，MSC通过减少多胺和胆固醇诱导的神经损伤而保护了MSA中的神经元丢失。