Determining nuclear localization of alpha-synuclein in mouse brains.
Determining nuclear localization of alpha-synuclein in mouse brains.
复制标题
DOI：
10.1016/j.neuroscience.2011.10.016
复制
发表时间：
2011-12-29
期刊：
影响因子：
3.3
通讯作者：
Zhou, Y.
中科院分区：
文献类型：
--
作者：
Huang, Z.;Xu, Z.;Wu, Y.;Zhou, Y.
α-突触核蛋白（α-Syn）是路易体的主要成分，路易体是帕金森病和其他神经系统疾病患者神经元中存在的异常蛋白质聚集体。尽管进行了深入的研究，但α-Syn在生理和病理过程中的体内作用尚未完全了解。本研究解决了目前关于α-Syn蛋白在脑中的核定位的争论。为了评估各种α-Syn抗体的特异性，我们比较了它们在野生型小鼠脑中与α-Syn敲除小鼠脑中的染色模式。在这里测试的五种不同的α-Syn抗体中，有两种在整个正常小鼠大脑中产生了强烈的核染色。然而，这两种抗体的核染色也存在于α-Syn敲除小鼠的神经元中。这提供了证据，表明核信号与α-Syn的存在没有特异性相关，而是由两种抗体与神经元核中某些未知抗原的交叉反应性引起的。在小鼠脑神经元中，内源性α-Syn蛋白主要定位于神经元突起和神经末梢，但仅以低水平存在于细胞体中。这与外源性表达的α-Syn在异源细胞的细胞质和细胞核中的一般均匀分布不同，并且表明α-Syn在神经元中的神经炎性富集可能是通过它们与神经元中某些结构或分子组分的特异性相互作用介导的。
Alpha-synuclein (α-Syn) is a major component of Lewy bodies, abnormal protein aggregates that are present in neurons of patients with Parkinson’s disease and other neurological disorders. Despite intensive investigation, the in vivo role of α-Syn in physiological and pathological processes is not fully understood. This study addresses a current debate on the nuclear localization of α-Syn protein in the brain. To assess the specificity of various α-Syn antibodies, we compared their staining patterns in wild type mouse brains with that of the α-Syn knock-out mice. Among five different α-Syn antibodies tested here, two generated intensive nuclear staining throughout the normal mouse brain. However, nuclear staining by these two antibodies was also present in neurons of the α-Syn knock-out mice. This provides evidence that the nuclear signal is not specifically related to the presence of α-Syn, but rather results from the cross-reactivity of the two antibodies to some unknown antigens in neuronal nuclei. In mouse brain neurons, endogenous α-Syn proteins are primarily localized to neuronal processes and nerve terminals but present only at low levels in the cell bodies. This is different from a generally uniform distribution of exogenously expressed α-Syn in both cytoplasm and nuclei of heterologous cells, and suggests that the neuritic enrichment of α-Syn in neurons may be mediated by their specific interactions with certain structural or molecular components in the neuropil.
登录
查看更多内容
影响因子：
16.2
作者：
Lin, Xian;Parisiadou, Loukia;Gu, Xing-Long;Wang, Lizhen;Shim, Hoon;Sun, Lixin;Xie, Chengsong;Long, Cai-Xia;Yang, Wan-Jou;Ding, Jinhui;Chen, Zsu Zsu;Gallant, Paul E.;Tao-Cheng, Jung-Hwa;Rudow, Gay;Troncoso, Juan C.;Liu, Zhihua;Li, Zheng;Cai, Huaibin
通讯作者：
Cai, Huaibin
影响因子：
3.3
作者：
Li, JY;Jensen, PH;Dahlström, A
通讯作者：
Dahlström, A
影响因子：
1.7
作者：
Bayer, TA;Jäkälä, P;Beyreuther, K
通讯作者：
Beyreuther, K
影响因子：
2.5
作者：
Lin, WL;DeLucia, MW;Dickson, DW
通讯作者：
Dickson, DW
影响因子：
3.3
作者：
Schell, H.;Hasegawa, T.;Kahle, P. J.
通讯作者：
Kahle, P. J.