Network analysis for identifying disease mechanisms and therapeutic targets for dementia

网络分析用于识别痴呆症的疾病机制和治疗靶点

• 批准号: 9788248
• 负责人: Judith Ann Potashkin
• 金额: $ 31.2万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-05-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788248
• 关键词: Accounting; Address; Adherence; Affect; Alzheimer' s Disease; Biological; Biological Markers; Blood; Characteristics; Chronic; Clinical; Clinical Management; Clinical Trials; Consumption; Data; Dementia; Diabetes Mellitus; Diagnosis; Dietary Practices; Disease; Early Diagnosis; Environment; Fishes; Fruit; Gene Chips; Genes; Genetic; Health; Impaired cognition; Individual; Insulin Resistance; Lewy Body Dementia; Life Style; Mediterranean Diet; Mental Depression; Messenger RNA; Meta-Analysis; Metabolic Diseases; Methods; Microarray Analysis; Molecular; Morphology; Nerve Degeneration; Neurodegenerative Disorders; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Olive oil preparation; Parkinson' s Dementia; Pathogenesis; Pathologic; Pathway Analysis; Pathway interactions; Patients; Poly(ADP-ribose) Polymerases; Prevalence; Progressive Supranuclear Palsy; Proteins; Public Health; RNA; Research; Research Design; Signal Pathway; Symptoms; System; Testing; Transcript; Vascular Dementia; Vegetables; accurate diagnosis; base; bioinformatics tool; brain health; cognitive development; dementia risk; diabetes risk; differential expression; epidemiology study; genetic risk factor; glucose metabolism; improved; individualized medicine; mild cognitive impairment; neurochemistry; prevent; therapeutic target; transcriptomics

Dementia is a growing public health concern with rising prevalence rates estimated to increase to 131 million within the next 3 decades. Accurate and early diagnosis of dementia is challenging with more than 50% of the cases undiagnosed. Dementia is associated with a wide spectrum of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease dementia, vascular dementia and mild cognitive impairment. These dementias share clinical symptoms and several genetic, neurochemical and morphological factors making the distinction very challenging. Despite the genetic and clinical overlap, the specific mechanism(s) leading to the different dementia subtypes is poorly understood. Diagnosis of the different subtypes of dementia is important given differences in disease course, treatment and clinical management. There remains an urgent need to differentiate these dementias and understand the mechanisms underlying their pathogenesis. A major risk factor for dementia and neurodegeneration is diabetes, a chronic metabolic disorder characterized by insulin resistance and altered glucose metabolism. Currently, there are no disease-modifying therapies for dementia, however, increasing evidence from epidemiological studies suggest that certain nutrients that reduce the risk of diabetes may be neuroprotective. For example, consumption of fish, olive oil, fruits and green leafy vegetables commonly present in a Mediterranean diet may prevent the development of cognitive decline and dementia, however the mechanisms by which these nutrients promote brain health are not yet understood. In this study, gene expression microarray data will be analyzed using unbiased system-based pathway and network analyses, based on genetic and protein interactions, to identify common and unique mechanisms underlying the pathogenesis of dementia, determine if these mechanisms underlie the association between dementia and diabetes and determine if adherence to a Mediterranean diet may be neuroprotective.

痴呆症是一个日益严重的公共卫生问题，患病率估计将增加到1.31亿 在未来的三十年内。痴呆症的准确和早期诊断具有挑战性，超过50%的患者 未确诊病例痴呆症与多种神经退行性疾病有关，包括 阿尔茨海默病、帕金森病痴呆、血管性痴呆和轻度认知障碍。这些 痴呆症具有共同的临床症状和几种遗传、神经化学和形态学因素， 区别很有挑战性。尽管遗传和临床重叠，但导致免疫缺陷的具体机制仍有待进一步研究。 不同的痴呆亚型知之甚少。诊断不同亚型的痴呆症是重要的 考虑到病程、治疗和临床管理的差异。仍然迫切需要 区分这些痴呆症并了解其发病机制。 痴呆症和神经退行性变的一个主要危险因素是糖尿病，这是一种慢性代谢紊乱， 胰岛素抵抗和葡萄糖代谢的改变。目前，没有疾病修饰疗法用于 然而，越来越多的流行病学研究证据表明， 降低患糖尿病的风险可能具有神经保护作用。例如，食用鱼、橄榄油、水果和 地中海饮食中常见的绿色多叶蔬菜可能会阻止认知功能障碍的发展。 然而，这些营养素促进大脑健康的机制还不清楚。 明白在本研究中，将使用基于无偏系统的方法分析基因表达微阵列数据 基于遗传和蛋白质相互作用的途径和网络分析，以确定共同和独特的 痴呆症发病机制的基础，确定这些机制是否是关联的基础 痴呆症和糖尿病之间的联系，并确定坚持地中海饮食是否可能具有神经保护作用。