Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb).
Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb).
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DOI：
10.1016/j.neuro.2013.07.010
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发表时间：
2013-12
期刊：
影响因子：
3.4
通讯作者：
Zawia, Nasser H.
中科院分区：
文献类型：
--
作者：
Bihaqi, Syed Waseem;Zawia, Nasser H.
晚发性阿尔茨海默病（LOAD）构成了大多数AD病例（约90%）。AD脑中存在的淀粉样变性和tau病理学似乎是散发性的。我们先前已经表明，婴儿期铅（Pb）暴露与老年时淀粉样前体蛋白（APP）及其β淀粉样蛋白（Aβ）产物表达和调节的变化有关。在这里，我们报告说，婴儿铅暴露升高的mRNA和蛋白质水平的tau蛋白，以及其转录调节因子，即特异性蛋白1和3（Sp1和Sp3）在老年灵长类动物。这些变化还伴随着位点特异性tau蛋白磷酸化的增强以及细胞周期蛋白依赖性激酶5（cdk 5）的mRNA和蛋白水平的增加。在婴儿时期接触铅的老年灵长类动物中，p35/p25蛋白质比例也发生了变化，存在更多的丝氨酸/苏氨酸磷酸酶活性。这些分子的改变有利于丰富的tau蛋白磷酸化和免疫反应性在前铅暴露的老年灵长类动物的额叶皮层。这些发现提供了更多的证据，表明神经退行性疾病可能是发育过程中发生的环境影响的产物。
Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (~90%). Amyloidosis and tau pathology, which are present in AD brains, appear to be sporadic in nature. We have previously shown that infantile lead (Pb) exposure is associated with a change in the expression and regulation of the amyloid precursor protein (APP) and its beta amyloid (Aβ) products in old age. Here we report that infantile Pb exposure elevated the mRNA and protein levels of tau as well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1 and Sp3) in aged primates. These changes were also accompanied by an enhancement in site-specific tau phosphorylation as well as an increase in the mRNA and protein levels of cyclin dependent kinase 5 (cdk5). There was also a change in the protein ratio of p35/p25 with more Serine/Threonine phosphatase activity present in aged primates exposed to Pb as infants. These molecular alterations favored abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with prior Pb exposure. These findings provide more evidence that neurodegenerative diseases may be products of environmental influences that occur during the development.
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影响因子：
5.3
作者：
Dosunmu, Remi;Alashwal, Hany;Zawia, Nasser H.
通讯作者：
Zawia, Nasser H.
影响因子：
3.4
作者：
Liu, Fei;Li, Bin;Gong, Cheng-Xin
通讯作者：
Gong, Cheng-Xin
DOI：
10.1073/pnas.94.1.298
发表时间：
1997-01-07
影响因子：
11.1
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
158.5
作者：
Canfield, RL;Henderson, CR;Lanphear, BP
通讯作者：
Lanphear, BP
影响因子：
16.2
作者：
Cruz, JC;Tseng, HC;Tsai, LH
通讯作者：
Tsai, LH