Molecular mechanisms of calcification: roles and opportunities in diseases of aging

钙化的分子机制：在衰老疾病中的作用和机会

• 批准号: 10628925
• 负责人: Francesca M Marassi
• 金额: $ 262.85万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628925
• 关键词: Age related macular degeneration; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Amyloid beta-Protein; Animal Disease Models; Animal Model; Baltimore; Biochemical; Biological; Biological Assay; Biophysics; Blindness; California; Cell model; Cells; Clinic; Data; Dementia; Deposition; Development; Diagnostic; Diphosphates; Disease; Disease Progression; Disease model; Etiology; Eye; Genetic; Goals; Hydroxyapatites; Image; In Situ; In Vitro; Individual; Label; Laboratories; Lipids; Magnetic Resonance Imaging; Maryland; Medical; Modeling; Molecular; Molecular Structure; NMR Spectroscopy; Pathway interactions; Process; Proteins; Reagent; Research; Research Personnel; Role; Sampling; Testing; Therapeutic; Tissues; Universities; Validation; Vitronectin; Work; aging population; calcification; calcification inhibitor; calcium phosphate; design; diagnostic strategy; effective therapy; extracellular; fluorescence imaging; imaging capabilities; in vivo; mineralization; novel; novel diagnostics; novel therapeutics; programs; protein purification; protein reconstitution; sensor; sensor technology; solid state nuclear magnetic resonance; synergism; tau Proteins; therapeutic development; three dimensional cell culture; tool

OVERALL SUMMARY Molecular mechanisms of calcification: roles and opportunities in diseases of aging. Ectopic calcification is a hallmark of major diseases of aging, including Age-Related Macular Degeneration (AMD) and Alzheimer's Disease (AD), disorders that each represent the leading causes of central vision loss and dementia among the aging population worldwide, and are currently incurable. There is an urgent need to understand disease mechanisms to enable the development of effective treatments. The overall goal of this Program Project is to elucidate the biological mechanisms of ectopic calcification and its role in the onset and etiology of diseases of aging, with particular focus on age-related macular degeneration (AMD) and Alzheimer’s disease (AD). The major components of the ectopic calcifications in AMD and AD are proteins, lipids and mineralized calcium phosphate, especially in the form of hydroxyapatite (HAP) and whitlockite (WHT), but the roles of these components in the calcification process and disease progression are not known. Four Projects, an administrative Core and a technical Core, will synergize to investigate ectopic calcification at the molecular, cellular and organismal levels, and build a comprehensive view of the key molecules and pathways responsible for this aging-related phenomenon. There are three overall Goals: (1) Elucidate the molecular mechanisms of ectopic calcification; (2) Develop diagnostic sensors for ectopic calcification; and (3) Dissect intra- and extra-cellular factors of ectopic calcification. The primary role of administrative Core will be to facilitate interactions among the investigators to generate a comprehensive view of calcification that could not be achieved by individual laboratories working alone.

总体汇总 钙化的分子机制：在衰老疾病中的作用和机会。异位 钙化是主要衰老疾病的标志，包括视网膜相关性黄斑变性（AMD）和 阿尔茨海默氏病（AD），每种疾病都代表中心视力丧失的主要原因， 老年痴呆症在世界范围内的老龄人口，目前无法治愈。迫切需要 了解疾病的机制，使有效的治疗方法的发展。总的目标是 计划项目是阐明异位钙化的生物学机制及其在发病中的作用， 老年性疾病的病因学，特别关注年龄相关性黄斑变性（AMD）， 阿尔茨海默病（AD）。AMD和AD中异位钙化的主要成分是蛋白质， 脂质和矿化的磷酸钙，特别是以羟基磷灰石（HAP）和白磷钙石的形式 (WHT)但这些成分在钙化过程和疾病进展中的作用尚不清楚。 四个项目，一个行政核心和一个技术核心，将协同研究异位钙化， 分子，细胞和有机体水平，并建立一个全面的看法，关键分子和 导致这种衰老相关现象的途径。有三个总体目标：（1）阐明 异位钙化的分子机制;（2）开发异位钙化的诊断传感器;（3） 解剖异位钙化的细胞内和细胞外因素。行政核心的主要作用是 促进研究者之间的互动，以产生一个全面的钙化视图， 由单独工作的实验室完成。