Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease.
Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease.
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DOI：
10.1016/j.bbrc.2015.08.076
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发表时间：
2015-10
影响因子：
3.1
通讯作者：
K. Tanji;Y. Miki;Atsushi Maruyama;J. Mimura;T. Matsumiya;F. Mori;T. Imaizumi;K. Itoh;K. Wakabayashi
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文献类型：
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作者：
K. Tanji;Y. Miki;Atsushi Maruyama;J. Mimura;T. Matsumiya;F. Mori;T. Imaizumi;K. Itoh;K. Wakabayashi
错误折叠和/或异常修饰的蛋白质的积累是许多神经退行性疾病的主要特征。在路易体病（LBD）（包括帕金森病和路易体痴呆）中，不溶性α-突触核蛋白广泛沉积在突触前末梢以及不同大脑区域的神经元细胞质中。众所周知，自噬-溶酶体系统是细胞内异常分子的有效降解途径。为了测试激活的自噬可以降解异常分子的可能性，我们在LBD模型中研究了海藻糖对α-突触核蛋白异常聚集的影响。海藻糖是由两个葡萄糖单元组成的天然二糖，具有自噬诱导剂的功能。与先前的研究一致，海藻糖增加了自噬体蛋白LC 3的水平，特别是培养细胞和小鼠脑中的脂化形式LC 3-II。此外，海藻糖增加了LBD模型小鼠脑中几种伴侣分子（如HSP 90和SigmaR 1）的水平。进一步研究表明，小鼠经口给予海藻糖后，洗涤剂不溶性α-突触核蛋白的水平受到抑制，尽管未观察到α-突触核蛋白异常聚集的明显变化。这些结果表明，海藻糖的口服摄入在聚集形成之前调节分子的倾向。
The accumulation of mis-folded and/or abnormally modified proteins is a major characteristic of many neurodegenerative diseases. In Lewy body disease (LBD), which includes Parkinson's disease and dementia with Lewy bodies, insoluble α-synuclein is widely deposited in the presynaptic terminals as well as in the neuronal cytoplasm in distinct brain regions. It is well known that the autophagy-lysosome system serves as an efficient degradation pathway for abnormal molecules within cells. To test the possibility that activated autophagy can degrade abnormal molecules, we investigated the effect of trehalose on abnormal aggregation of α-synuclein in a model of LBD. Trehalose is a natural disaccharide composed of two glucose units and functions as an autophagy inducer. Consistent with previous studies, trehalose increased level of the autophagosomal protein LC3, especially a lipidated form LC3-II in cultured cells and mice brain. Also, trehalose increased levels of several chaperon molecules, such as HSP90 and SigmaR1, in the brains of LBD model mice. Further studies revealed that level of detergent-insoluble α-synuclein was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of α-synuclein. These results suggest that the oral intake of trehalose modulates propensity of molecules prior to aggregation formation.