Α-synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexaenoic acid in a mouse model for Parkinson's disease.
Α-synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexaenoic acid in a mouse model for Parkinson's disease.
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DOI：
10.1111/j.1750-3639.2011.00530.x
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Sharon R
中科院分区：
文献类型：
--
作者：
Yakunin E;Loeb V;Kisos H;Biala Y;Yehuda S;Yaari Y;Selkoe DJ;Sharon R
α-突触核蛋白（α-Syn）是一种神经元蛋白，在帕金森病和相关的突触核蛋白病中进行性积累。为了确定影响α-Syn神经病理学的细胞因子，我们以前报道过多不饱和脂肪酸（PUFA）促进培养细胞中α-Syn的寡聚化和聚集。我们现在报道二十二碳六烯酸（DHA）a 22：6 PUFA通过激活视黄酸X受体（RXR）和过氧化物酶体增殖物激活受体γ 2（PPAR γ 2）影响α-Syn寡聚化。此外，我们还发现，大脑DHA水平的饮食变化会影响人α-Syn中导致帕金森病的A53T突变转基因小鼠的α-Syn细胞病理学。富含二十二碳六烯酸（RXR的活化配体）的饮食增加了可溶性和不溶性神经元α-Syn的积累、神经炎性损伤和星形胶质细胞增多。相反，α-Syn的异常积累及其有害影响被低水平的膳食二十二碳六烯酸显著减弱。我们的研究结果表明，通过升高脑多不饱和脂肪酸水平获得的活化RXR/PPAR γ 2在α-Syn神经病理学中发挥作用。
α-synuclein (α-Syn) is a neuronal protein that accumulates progressively in Parkinson’s disease and related synucleinopathies. Attempting to identify cellular factors that affect α-Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α-Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA) a 22:6 PUFA affects α-Syn oligomerization by activating retinoic X receptor (RXR) and peroxisome proliferator-activated receptor γ2 (PPARγ2). In addition, we show that dietary changes in brain DHA levels affect α-Syn cytopathology in mice transgenic for the Parkinson’s disease-causing A53T mutation in human α-Syn. A diet enriched in docosahexaenoic acid, an activating ligand of RXR, increased the accumulation of soluble and insoluble neuronal α-Syn, neuritic injury and astrocytosis. Conversely, abnormal accumulations of α-Syn and its deleterious effects were significantly attenuated by low dietary docosahexaenoic acid levels. Our results suggest a role for activated RXR/PPARγ 2, obtained by elevated brain polyunsaturated fatty acids levels, in α-Syn neuropathology.
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影响因子：
16.2
作者：
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