Protective effects of trehalose against Mn-induced α-synuclein oligomerization in mice: Involvement of oxidative stress and autophagy.
Protective effects of trehalose against Mn-induced α-synuclein oligomerization in mice: Involvement of oxidative stress and autophagy.
复制标题
海藻糖对小鼠中锰诱导的α-突触核蛋白寡聚化的保护作用：氧化应激和自噬的参与。
DOI：
10.1002/tox.22842
复制
发表时间：
2020
影响因子：
4.5
通讯作者：
Xu Bin
中科院分区：
文献类型：
--
作者：
Jing Meng-Jiao;Liu Kuan;Liu Chang;Yan Dong-Ying;Ma Zhuo;Wang Can;Deng Yu;Liu Wei;Xu Bin
众所周知，过度暴露于锰（Mn）会诱导α -突触核蛋白（α - Syn）寡聚化，这归因于α - Syn蛋白的氧化损伤。海藻糖已被证明可以诱导自噬并作为一种化学伴侣，但关于其对Mn诱导的α‐Syn寡聚化的影响的报道很少。在这项研究中，我们在锰中毒小鼠模型中使用不同浓度的海藻糖（2%和4% (g/vol [mL])）来研究海藻糖是否能有效地干扰Mn诱导的α‐Syn寡聚。暴露于Mn 6周后，氧化应激和自噬均被激活，导致小鼠脑组织α‐Syn寡聚化和神经元细胞损伤。我们的研究结果还表明，海藻糖预处理显著降低α‐Syn蛋白的氧化损伤，增加自噬激活。这些发现清楚地表明海藻糖可以通过其抗氧化和诱导自噬的作用来减轻Mn诱导的α - Syn寡聚和神经元细胞损伤。
Overexposure to manganese (Mn) is widely known to induce alpha‐synuclein (α‐Syn) oligomerization, which has been attributed to the oxidative damage of α‐Syn protein. Trehalose has been shown to induce autophagy and serve as a chemical chaperone, but little information has been reported about its effect on Mn‐induced α‐Syn oligomerization. In this study, we investigate whether trehalose can effectively interfere with Mn‐induced α‐Syn oligomerization, using different concentrations of trehalose (2% and 4% (g/vol [mL])) in a mouse model of manganism. After 6 weeks of exposure to Mn, both oxidative stress and autophagy were activated and resulted in α‐Syn oligomerization and neuronal cell damage in the mouse brain tissue. Our results also revealed that pretreatment with trehalose significantly reduced the oxidative damage to α‐Syn protein and increased autophagy activation. These findings clearly demonstrated that trehalose can relieve Mn‐induced α‐Syn oligomerization and neuronal cell damage through its anti‐oxidative and autophagy‐inducing effects.