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Advances in the Pathogenesis of Alzheimer’s Disease:Focusing on Tau-Mediated Neurodegeneration

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Translational Neurodegeneration 2012年第1期1卷 192-198页

作者： Yale Duan Suzhen Dong Feng Gu yinghe hu Zheng Zhao Key Laboratory of Brain Functional Genomics Ministry of EducationShanghai Key Laboratory of Brain Functional GenomicsEast China Normal University3663 Zhongshan Road(N)Shanghai 200062China Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development East China Normal UniversityShanghai 200062China

In addition to senile plaques and cerebral amyloid angiopathy,the hyperphosphorylation of tau protein and formation of intraneuronal neurofibrillary tangles(NFTs)represents another neuropathological hallmark in AD *** is a microtubule-associated protein and localizes predominantly in the axons of neurons with the primary function in maintaining microtubules *** the balance between tau phosphorylation and dephosphorylation is changed in favor of the former,tau is hyperphosphorylated and the level of the free tau fractions *** hyperphosphorylation of tau protein and formation of NFTs represent a characteristic neuropathological feature in AD *** have discussed the role of Aβin AD in our previous review,this review focused on the recent advances in tau-mediated AD pathology,mainly including tau hyperphosphorylation,propagation of tau pathology and the relationship between tau and Aβ.

关键词： Alzheimer’s disease Tau A-beta Tauopathy Tau hyperphosphorylation Intraneuronal neurofibrillary tangles

Global view of transcriptome in the brains of aged NR2B transgenic mice

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Neural Regeneration Research 2013年第29期8卷 2734-2743页

作者： Chunxia Li Men Su huimin Wang yinghe hu Key Lab of Brain Functional Genomics MOE&STCSMInstitute of Cognitive NeuroscienceEast China Normal University Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development East China Normal University

NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as well as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.

关键词： neural regeneration memorygrowth factor grants-supportedNR2B transgenic mice aging gene expression P53 insulin-likepaper neuroregeneration

Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth

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Journal of Genetics and Genomics 2012年第8期39卷 375-384页

作者： Jin Wu Zongli Zhou yinghe hu Suzhen Dong Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development East China Normal University Shanghai 200062 China Institute of Chemical and Translational Genomics East China Normal University Shanghai 200062 China Shanghai Institute of Brain Functional Genomics MOE & STCSM Key Lab of Brain Functional Genomics East China Normal University Shanghai 200062 China

Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the Gl-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.

关键词： GPR41 Butyrate HDAC inhibitor Anti-proliferation Cell cycle arrest

Advances in the pathogenesis of Alzheimer’s disease:a re-evaluation of amyloid cascade hypothesis

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Translational Neurodegeneration 2012年第1期1卷 140-151页

作者： Suzhen Dong Yale Duan yinghe hu Zheng Zhao Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development East China Normal UniversityShanghai 200062China Institute of Chemical and Translational Genomics East China Normal UniversityShanghai 200062China Key Laboratory of Brain Functional Genomics Ministry of EducationShanghai Key Laboratory of Brain Functional GenomicsEast China Normal University3663 Zhongshan Road(N)Shanghai 200062China

Alzheimer’s disease(AD)is a common neurodegenerative disease characterized clinically by progressive deterioration of memory,and pathologically by histopathological changes including extracellular deposits of amyloid-beta(A-beta)peptides forming senile plaques(SP)and the intracellular neurofibrillary tangles(NFT)of hyperphosphorylated tau in the *** review focused on the new developments of amyloid cascade hypothesis with details on the production,metabolism and clearance of A-beta,and the key roles of some important A-beta-related genes in the pathological processes of *** most recent research advances in genetics,neuropathology and pathogenesis of the disease were also discussed.

关键词： Alzheimer’s disease A-beta APP BACE1 Presenilins ApoE Neprilysin/insulin-degrading enzyme

3-[3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine oxalate,a novel xanomeline derivative,improves neural cells proliferation and survival in adult mice

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Neural Regeneration Research 2012年第1期7卷 24-30页

作者： Xiaoliang Zhang Qiang Gong Shuang Zhang Lin Wang yinghe hu Haiming Shen Suzhen Dong Key Laboratory of Brain Functional Genomics Ministry of Education East China Normal University Shanghai 200062 China Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development Institute for Advanced Interdisciplinary Research East China Normal University Shanghai 200062 China Institute of Aviation Medicine Civil Aviation University of China Tianjin 300300 China

The present study analyzed the influence of 3-[3-（3-florophenyl-2-propyn-l-ylthio）-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-l-methylpyridine oxalate （EUK1001）, a novel xanomeline derivative of the M1/M4 receptor agonist, on hippocampal neurogenesis in adult C57BL6 mice. Results showed that 15-day EUK1001 treatment via intraperitoneal injection promoted neural cell proliferation in the dentate gyrus, although cell differentiation did not change. The majority of bromodeoxyuridine-positive cells co-expressed the immature neuronal marker doublecortin. In addition, the level of neurogenesis in the subventricular zone was not altered. Brain-derived neurotrophic factor mRNA expression was up-regulated following EUK1001 treatment, but no change was observed in expression of camp-responsive element binding protein 1, paired box gene 6, vascular endothelial growth factor alpha, neurogenic differentiation factor 1, and wingless-related mouse mammary tumor virus integration site 3A mRNA. These experimental findings indicated that EUK1001 enhanced proliferation and survival of hippocampal cells, possibly by increasing brain-derived neurotrophic factor expression.

关键词： EUK1001 brain-derived neurotrophic factor MjM4 receptor neural regeneration proliferation survival

道德和个人领域儿童情绪理解的发展特点及对其亲社会行为的影响

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心理学探新 2017年第1期37卷 41-47页

作者：周双珠陈英和胡竹菁江西师范大学心理学院南昌330022 北京师范大学心理学院北京100875

本研究探讨了173名4~10岁儿童在道德领域和个人领域情绪理解的发展变化特点,以及儿童情绪理解能力的发展与其亲社会行为的关系。结果表明:(1)在主要情绪预测中,随着年龄的增长,儿童越来越多的预测违反规则感到高兴。从8岁开始,儿童预测... 详细信息

本研究探讨了173名4~10岁儿童在道德领域和个人领域情绪理解的发展变化特点,以及儿童情绪理解能力的发展与其亲社会行为的关系。结果表明:(1)在主要情绪预测中,随着年龄的增长,儿童越来越多的预测违反规则感到高兴。从8岁开始,儿童预测违反道德领域的规则比违反个人领域的规则会更不高兴。(2)在次要情绪预测中,在道德领域,随着年龄的增长,越来越多的儿童预测"违反感觉不高兴"。在个人领域,预测"违反感觉不高兴"的人数在10岁组出现下降。(3)8~10岁组儿童道德领域的情绪理解能显著预测其亲社会行为,儿童预测违反道德规则时的情绪预测越积极,其教师评定的亲社会行为水平越低。这些结果表明随着年龄的增长,儿童展现出越来越丰富、复杂的情绪理解能力,并且儿童道德领域的情绪理解能力能显著预测儿童日常生活中的亲社会行为。

关键词：道德领域个人领域情绪理解亲社会行为心理理论社会领域理论

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激光微束照射对核仁基因的研究

光电子.激光 1985年第2期 1-4页

作者：粱宏胡应和中国科学院遗传研究所

核仁是细胞中一种非常重要的细胞器。细胞生物学、生物化学和遗传方面的研究都表明,核仁里含有rDNA,而几乎全部细胞里的rDNA都是在核仁里合成,然后传递到细胞核和细胞质里。核仁是在细胞中某些

关键词：核仁子细胞间期细胞 PTK 激光微束细胞核核(细胞学) 基因

复合滤材的结构设计及其对PM2.5的防护性能

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丝绸 2018年第7期55卷 28-34页

作者：娄辉清王利娜闫新陈增斌邵丕健李海伟胡颖荷河南工程学院纺织学院郑州450007 纺织服装产业河南省协同创新中心郑州450007 河南工程学院材料与化学工程学院郑州450007

为获得具有过滤效率高、防护性能好且制备成本低的PM2.5复合滤材,采用环保型黏合剂如明胶和羧甲基纤维素钠(CMC)的复配溶液,对纺黏非织造布(S)和熔喷非织造布(M)进行层间点黏合复合。实验结果表明,层间黏合方式和黏结点间距对复合滤材... 详细信息

为获得具有过滤效率高、防护性能好且制备成本低的PM2.5复合滤材,采用环保型黏合剂如明胶和羧甲基纤维素钠(CMC)的复配溶液,对纺黏非织造布(S)和熔喷非织造布(M)进行层间点黏合复合。实验结果表明,层间黏合方式和黏结点间距对复合滤材的过滤性能和透气性有较大的影响;采用间隔3 cm的点黏合方式制备的SMS型复合滤材,对NaCl气溶胶的过滤效率可到达98%以上且阻力压降在120 Pa以下;所制备的SMS型复合滤材在不同污染天气条件下对PM2.5的过滤效率均在95%以上,且容尘量随污染程度增加而增大。

关键词：复合滤材化学黏合点黏合 PM2.5 过滤防护性能

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氩离子激光显微照射对细胞损伤的研究

中国激光 1984年第4期 239-243页

作者：陆仲康胡应和邓燕华王兰岚宋桂英孙宝霞梁宏中国科学院遗传研究所

利用YW-1型氩离子激光显微仪对PTK1、PTK2和人红血球细胞进行显微照射,最小有效损伤光斑仅0.5微米。细胞化学分析表明,在不用任何活性染料敏化细胞的情况下,激光照射能够破坏核仁内的DNA和RNA。

关键词：细胞核仁 DNA 激光照射氩离子激光激光波长