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Novel surface-modified bioresorbable zinc-based stent materials

新型表面改性生物可吸收锌基支架材料

基本信息

批准号：
10282711
负责人：
Yadong Wang
金额：
$ 39.54万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10282711
关键词：
Abeta synthesis Achievement Address Adverse effects Affect Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Amygdaloid structure Amyloid beta-42 Amyloid beta-Protein Animal Model Astrocytes Binding Biological Biological Assay Brain Brain region Brain-Derived Neurotrophic Factor Caspase Cell Line Cell Survival Cell physiology Cells Chelating Agents Chronic Clinical Trials Complex Dementia Deposition Development Edetic Acid Elderly Elements Emotional Stability Fluorescence Growth Health Hippocampus (Brain)Histocompatibility Antigens Class II Homeostasis Human Immune Incubated Inflammation Inflammatory Investigation Ions Lead Learning Link Maintenance Measures Mediating Memory Metals Microglia Molecular Conformation Neocortex Nervous system structure Neurodegenerative Disorders Neurofibrillary Tangles Neuroglia Neurons Nitric Oxide Synthase Oxidation-Reduction Pathogenesis Pathology Pathway interactions Pericytes Play Population Process Proteins Rattus Reporting Risk Factors Role Senile Plaques Signal Transduction Spectrum Analysis Stents Structure Surface Testing Thinness Toxic effect Trace Elements Zinc Zinc deficiency abeta accumulation abeta oligomer abeta toxicity base brain cell brain dysfunction brain endothelial cell cell type cerebrovascular clinical application clinical investigation cytotoxicity design drug discovery immune function mitochondrial dysfunction mouse model neocortical nervous system disorder neurotrophic factor novel novel strategies pre-clinical success tau Proteins tau phosphorylation therapeutic target

项目摘要

Summary: “Zinc-Aβ interaction and its toxicity on brain cells” Zinc is essential for health and is the second abundant trace element in human brain. Zinc dyshomeostasis is implicated in the elderly population and Alzheimer’s disease (AD) which has many other risk factors besides Aβ and tau. Emerging evidence demonstrated that zinc also plays an important role in the pathogenesis of AD such as Aβ production and aggregation, tau phosphorylation, redox homeostasis, and brain-derived neurotrophic factor (BDNF) signaling. Zinc dyshomeostasis could be a therapeutic target for AD treatment. However, there are still controversies on the zinc concentration alteration, and the effect of zinc overload or zinc deficiency in AD patients, mouse models and cell lines. Providing these significant discrepancies across reported studies, more carefully-designed cellular, preclinical and clinical investigations are needed to portray a clearer picture of zinc’s role in AD development before clinical applications. Toward this end, we aim to investigate the interactions between zinc and Aβ, effect of zinc binding on Aβ aggregation, and the potential toxicity of Zn-chelated Aβ (ZnAβ) species on a variety of brain cells including neurons, microglia, astrocytes, and cerebrovascular cells in this one- year supplemental project.

综述：《锌与β的相互作用及其对脑细胞的毒性》锌是人体必需的健康元素，是人脑中第二丰富的微量元素。锌代谢紊乱是与老年人群和阿尔茨海默病(AD)有关，阿尔茨海默病(AD)除了β外还有许多其他危险因素还有陶。新的证据表明，锌在AD的发病机制中也起着重要作用。 AS Aβ的产生和聚集、tau磷酸化、氧化还原动态平衡和脑源性神经营养因子(BDNF)信号转导。锌代谢紊乱可作为AD治疗的靶点。然而，在那里关于锌浓度的变化，以及锌超载或缺锌的影响，目前仍存在争议 AD患者、小鼠模型和细胞系。提供了这些报告研究中的显著差异，需要更仔细地设计细胞、临床前和临床研究，才能更清楚地描绘出锌在阿尔茨海默病临床应用前的作用。为此，我们的目标是研究相互作用锌与Aβ之间的相互作用、锌结合对Aβ聚集的影响以及锌螯合Aβ(ZNAβ)的潜在毒性包括神经元、小胶质细胞、星形胶质细胞和脑血管细胞在内的各种脑细胞上的物种- 年度补充项目。