Neuroserpin up-regulation in the Alzheimer's disease brain is associated with elevated thyroid hormone receptor-β1 and HuD expression.
Neuroserpin up-regulation in the Alzheimer's disease brain is associated with elevated thyroid hormone receptor-β1 and HuD expression.
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DOI：
10.1016/j.neuint.2013.08.010
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发表时间：
2013-11
影响因子：
4.2
通讯作者：
Seeds NW
中科院分区：
文献类型：
--
作者：
Subhadra B;Schaller K;Seeds NW
神经丝氨酸蛋白酶是脑组织纤溶酶原激活物（tPA）的主要抑制剂，在阿尔茨海默病（AD）中已被证实表达上调。抑制tPA活性导致脑内纤溶酶水平降低，纤溶酶是脑内淀粉样蛋白及其斑块降解和清除的主要酶之一。甲状腺激素是已知的少数能增强神经元中神经丝氨酸蛋白表达的因素之一。甲状腺激素通过结合其受体THR1α和THR1β作用于神经元，然后在细胞核中上调包括rna结合蛋白HuD在内的许多基因的表达。HuD在转录后通过稳定其mrna来增强包括神经丝氨酸在内的许多蛋白质的表达。通过western blotting将一系列阿尔茨海默病脑组织与年龄匹配的对照组脑组织进行比较，观察其神经丝氨酸蛋白、THRβ1和HuD的表达。神经丝氨酸蛋白升高的阿尔茨海默病脑组织中THRβ1和HuD的表达也增加。两两分析显示，神经丝氨酸肽、thrr β1与HuD水平存在显著相关p值；提示阿尔茨海默病患者大脑中神经丝氨酸蛋白的上调可能是由于这些个体中甲状腺激素反应系统的激活。这些发现为甲状腺激素紊乱和阿尔茨海默病之间的潜在关系提供了证据。
Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain, has been shown to be up-regulated in Alzheimer’s disease (AD). Inhibition of tPA activity leads to reduced brain levels of plasmin, one of the main enzymes responsible for the degradation and clearance of amyloid-beta and its plaques from the brain. Thyroid hormone is one of the few factors known to enhance expression of neuroserpin in neurons. Thyroid hormone acts on neurons by binding to its receptors THR1α and THR1β, which then function in the nucleus to up-regulate the expression of numerous genes including the RNA-binding protein HuD. HuD acts post-transcriptionally to enhance expression of numerous proteins including neuroserpin by stabilizing their mRNAs. A series of Alzheimer’s disease brain tissues were compared to age-matched control brains for their expression of neuroserpin, THRβ1 and HuD by western blotting. Alzheimer’s disease brain tissues with elevated neuroserpin protein also showed increased expression of THRβ1 and HuD. Pair-wise analyses showed significant correlation p-values between neuroserpin, THRβ1 and HuD levels; suggesting that the up-regulation of neuroserpin in Alzheimer’s disease brain may result from an activation of the thyroid hormone response system in these individuals. These findings provide evidence for a potential relationship between thyroid hormone disorders and Alzheimer’s disease.
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影响因子：
14.9
作者：
Bolognani F;Contente-Cuomo T;Perrone-Bizzozero NI
通讯作者：
Perrone-Bizzozero NI
DOI：
10.3233/jad-2009-0967
发表时间：
2009
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Amadio M;Pascale A;Wang J;Ho L;Quattrone A;Gandy S;Haroutunian V;Racchi M;Pasinetti GM
通讯作者：
Pasinetti GM
影响因子：
4.7
作者：
Fabbro, Shay;Schaller, Kristin;Seeds, Nicholas W.
通讯作者：
Seeds, Nicholas W.
影响因子：
4.5
作者：
Bensenor, Isabela M.;Lotufo, Paulo A.;Scazufca, Marcia
通讯作者：
Scazufca, Marcia
DOI：
10.1111/j.1582-4934.2011.01394.x
发表时间：
2012-04-01
影响因子：
5.3
作者：
Barker, Rachel;Kehoe, Patrick G.;Love, Seth
通讯作者：
Love, Seth