OBJECTIVE： To quantitatively evaluate the association between tau genetic polymorphism （H1 and H2） and susceptibility to sporadic progressive supranuclear palsy （PSP）. DATA SOURCES： Relevant Medical Subject Head...OBJECTIVE： To quantitatively evaluate the association between tau genetic polymorphism （H1 and H2） and susceptibility to sporadic progressive supranuclear palsy （PSP）. DATA SOURCES： Relevant Medical Subject Heading terms and text words were used to identify articles from MEDLINE （1966/2010-07）, EMBASE （1984/2010-07）, and Chinese National Knowledge Infrastructure （1979/2010）, as well as references of the retrieved articles. STUDY SELECTION： The selected articles met the following criteria： sporadic PSP case group and healthy control group, as well as genotype frequency （H1/H1 and H1/H2 ＋ H2/H2） in cases and controls. Genotype distribution in the control groups was tested using the Hardy-Weinberg Equilibrium （HWE）. Articles irrelevant to HWE were excluded, and a forest plot was performed to combine all selected articles with Review Manager （Version 5.0）. MAIN OUTCOME MEASURES： The summary odds ratios arid corresponding 95% confidence intervals （95%CI） for tau polymorphism （H1/H1 and H1/H2 ＋ H2/H2） between sporadic PSP case and healthy control groups were estimated using the fixed effects model to assess whether tau genetic polymorphism is associated with sporadic PSP susceptibility. RESULTS： According to inclusion and exclusion criteria, a total of 16 articles, which included 1 337 sporadic PSP cases and 2 073 controls, were used in the study. Two articles were excluded because of deviation from HWE in the control groups. The combined result, based on all studies, showed a significant difference in genotype distribution between cases and controls： H1H1 vs. H1H2 ＋ H2H2 （odds ratio （OR） = 4.98, 95%C1： 3.97-6.23, P 〈 0.01）. Stratifying for geographic distribution of PSP, sporadic PSP cases exhibited a significantly higher frequency of H1H1 genotypes than controls in the United States （OR = 4.07, 95%C/： 3.16-5.25, P 〈 0.01） and Europe （OR = 8.60, 95%C1： 5.05-14.64, P〈 0.01）. CONCLUSION： Tau genetic polymorphism is associated with sporadic PSP susceptibility, and geographic distribution might play a role in tau genetic polymorphism and sporadic PSP susceptibility.展开更多
A predicted tau glutathione S-transferase(GST) subunit encoding gene,named GhGST,was isolated from Gossypium hirsutum with RACE method from SSH library based on Verticillium
A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sp...A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT- the 3＇ and 5＇ untranslated regions as well as introns 9, 10, 11, and 12 - by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A 〉 G in intron 9 and 123972 T 〉 A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A 〉 G and/or the 123972 T 〉 A variant was younger than that in patients without either genetic variation. Moreover, the pa- tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.展开更多
目的:探讨外源性降钙素基因相关肽(Calcitonin gene related peptide,CGRP)对局灶性脑缺血再灌注大鼠顶叶皮质tau蛋白过度磷酸化的影响。方法:用线栓法制作局灶性脑缺血再灌注模型,应用免疫组织化学SABC法、Western Blotting和图像分析...目的:探讨外源性降钙素基因相关肽(Calcitonin gene related peptide,CGRP)对局灶性脑缺血再灌注大鼠顶叶皮质tau蛋白过度磷酸化的影响。方法:用线栓法制作局灶性脑缺血再灌注模型,应用免疫组织化学SABC法、Western Blotting和图像分析方法检测大鼠顶叶皮质tau蛋白在Ser199/202位点磷酸化程度和总tau蛋白表达、以及CGRP对缺血神经元tau蛋白过度磷酸化的影响。结果:缺血再灌注顶叶皮质tau蛋白在Ser199/202位点磷酸化水平和总tau蛋白显著升高(P<0.05);CGRP组大鼠顶叶皮质tau蛋白在Ser199/202位点磷酸化水平显著低于缺血再灌注组,总tau也降低(P<0.05)。结论:CGRP明显减轻局灶性脑缺血再灌注大鼠顶叶皮质tau蛋白磷酸化程度,降低tau蛋白磷酸化水平可能对缺血神经元起保护作用。展开更多
Alzheimer＇s disease（AD） is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by...Alzheimer＇s disease（AD） is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β（Aβ） peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein（APP） processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic（Tg） mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type（WT） mice, contributing to the development of an Alzheimer＇s-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD.展开更多
钙调神经磷酸酶(calcineurin,CN)作为机体中的一种丝/苏氨酸磷酸酶,在关键的生物学过程中发挥着重要作用.RCANs(regulators of calcineurin)是CN的一类内源调节因子,其家族成员在细胞中能够通过与CN在结构上的相互结合,起到调节CN活性...钙调神经磷酸酶(calcineurin,CN)作为机体中的一种丝/苏氨酸磷酸酶,在关键的生物学过程中发挥着重要作用.RCANs(regulators of calcineurin)是CN的一类内源调节因子,其家族成员在细胞中能够通过与CN在结构上的相互结合,起到调节CN活性的作用.而近来研究发现,该调节因子还可参与到CN-NFAT信号通路中发挥功能,从而与CN依赖的生理和病理过程的调控密切相关.因此,有必要对RCAN基因、RCANs蛋白与CN的相互作用以及该家族成员在病理条件下的重要功能作一个较为全面的综述,这些基础研究工作的进展将有助于为寻找新的疾病治疗方法和药物开辟新的途径.展开更多
文摘OBJECTIVE： To quantitatively evaluate the association between tau genetic polymorphism （H1 and H2） and susceptibility to sporadic progressive supranuclear palsy （PSP）. DATA SOURCES： Relevant Medical Subject Heading terms and text words were used to identify articles from MEDLINE （1966/2010-07）, EMBASE （1984/2010-07）, and Chinese National Knowledge Infrastructure （1979/2010）, as well as references of the retrieved articles. STUDY SELECTION： The selected articles met the following criteria： sporadic PSP case group and healthy control group, as well as genotype frequency （H1/H1 and H1/H2 ＋ H2/H2） in cases and controls. Genotype distribution in the control groups was tested using the Hardy-Weinberg Equilibrium （HWE）. Articles irrelevant to HWE were excluded, and a forest plot was performed to combine all selected articles with Review Manager （Version 5.0）. MAIN OUTCOME MEASURES： The summary odds ratios arid corresponding 95% confidence intervals （95%CI） for tau polymorphism （H1/H1 and H1/H2 ＋ H2/H2） between sporadic PSP case and healthy control groups were estimated using the fixed effects model to assess whether tau genetic polymorphism is associated with sporadic PSP susceptibility. RESULTS： According to inclusion and exclusion criteria, a total of 16 articles, which included 1 337 sporadic PSP cases and 2 073 controls, were used in the study. Two articles were excluded because of deviation from HWE in the control groups. The combined result, based on all studies, showed a significant difference in genotype distribution between cases and controls： H1H1 vs. H1H2 ＋ H2H2 （odds ratio （OR） = 4.98, 95%C1： 3.97-6.23, P 〈 0.01）. Stratifying for geographic distribution of PSP, sporadic PSP cases exhibited a significantly higher frequency of H1H1 genotypes than controls in the United States （OR = 4.07, 95%C/： 3.16-5.25, P 〈 0.01） and Europe （OR = 8.60, 95%C1： 5.05-14.64, P〈 0.01）. CONCLUSION： Tau genetic polymorphism is associated with sporadic PSP susceptibility, and geographic distribution might play a role in tau genetic polymorphism and sporadic PSP susceptibility.
文摘A predicted tau glutathione S-transferase(GST) subunit encoding gene,named GhGST,was isolated from Gossypium hirsutum with RACE method from SSH library based on Verticillium
基金funded by the National Natural Science Foundation of China,No.30560042 and 81260194Jiangxi Provincial Health Bureau of Science and Technology Program,No.20111028
文摘A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT- the 3＇ and 5＇ untranslated regions as well as introns 9, 10, 11, and 12 - by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A 〉 G in intron 9 and 123972 T 〉 A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A 〉 G and/or the 123972 T 〉 A variant was younger than that in patients without either genetic variation. Moreover, the pa- tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.
文摘目的:探讨外源性降钙素基因相关肽(Calcitonin gene related peptide,CGRP)对局灶性脑缺血再灌注大鼠顶叶皮质tau蛋白过度磷酸化的影响。方法:用线栓法制作局灶性脑缺血再灌注模型,应用免疫组织化学SABC法、Western Blotting和图像分析方法检测大鼠顶叶皮质tau蛋白在Ser199/202位点磷酸化程度和总tau蛋白表达、以及CGRP对缺血神经元tau蛋白过度磷酸化的影响。结果:缺血再灌注顶叶皮质tau蛋白在Ser199/202位点磷酸化水平和总tau蛋白显著升高(P<0.05);CGRP组大鼠顶叶皮质tau蛋白在Ser199/202位点磷酸化水平显著低于缺血再灌注组,总tau也降低(P<0.05)。结论:CGRP明显减轻局灶性脑缺血再灌注大鼠顶叶皮质tau蛋白磷酸化程度,降低tau蛋白磷酸化水平可能对缺血神经元起保护作用。
基金supported by grants PFB (Basal Financing Program) 12/2007 from the Basal Centre for Excellence in Science and Technology and FONDECYT,No.1120156(to NCI)a pre-doctoral fellowship from the National Commission of Science and Technology of Chile(CONICYT)(to CTR)
文摘Alzheimer＇s disease（AD） is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β（Aβ） peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein（APP） processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic（Tg） mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type（WT） mice, contributing to the development of an Alzheimer＇s-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD.
文摘钙调神经磷酸酶(calcineurin,CN)作为机体中的一种丝/苏氨酸磷酸酶,在关键的生物学过程中发挥着重要作用.RCANs(regulators of calcineurin)是CN的一类内源调节因子,其家族成员在细胞中能够通过与CN在结构上的相互结合,起到调节CN活性的作用.而近来研究发现,该调节因子还可参与到CN-NFAT信号通路中发挥功能,从而与CN依赖的生理和病理过程的调控密切相关.因此,有必要对RCAN基因、RCANs蛋白与CN的相互作用以及该家族成员在病理条件下的重要功能作一个较为全面的综述,这些基础研究工作的进展将有助于为寻找新的疾病治疗方法和药物开辟新的途径.
