Identifying New Immunomodulatory Targets for Alzheimers and Other Neurodegenerative Diseases

确定阿尔茨海默病和其他神经退行性疾病的新免疫调节靶点

基本信息

批准号：
9766179
负责人：
Benjamin Jacob Doranz
金额：
$ 20.38万
依托单位：
INTEGRAL MOLECULAR
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：
2018-09-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9766179
关键词：
Abbreviations Alzheimer&apos s Disease American Antibodies Area Astrocytes Binding Biosensor Cause of Death Cells Clinical Trials Communication Disease Disease Progression Generations Genetic Goals Health Human Immune Immunooncology Intervention Ligands Link Membrane Membrane Proteins Microglia Molecular Molecular Conformation Neurodegenerative Disorders Neurofibrillary Tangles Neuroimmune Pathologic Pharmaceutical Preparations Phenotype Prevalence Process Proteins Proteome Receptor Cell Risk Senile Plaques Specificity Structure Surface T-Lymphocyte Technology Testing Therapeutic Therapeutic Clinical Trial TimeLine Titrations Treatment Efficacy Virus Receptors Work cell type disability effective therapy experimental study genome wide association study immune checkpoint immunoregulation neuroregulation new therapeutic target novel oncology prevent receptor response risk minimization screening tau Proteins therapeutic target therapy development

项目摘要

ABSTRACT Alzheimer's disease (AD) and other neurodegenerative diseases are a major cause of death and disability for older Americans, with a US prevalence of more than 6.5 million. As AD currently cannot be cured or prevented, there is an urgent need for effective treatments targeting underlying disease processes. A major roadblock in treatment development has been the lack of good targets. Although pathologically important, amyloid beta plaques and tau tangles are not easily druggable, and clinical trials of therapeutics targeting these proteins directly have largely failed. Recent genome-wide association studies have identified a link between a growing number of modulatory proteins on neuroimmune cells, particularly on the surface of microglia and astrocytes, that are linked to the risk of developing AD. The identification of new proteins with neuroimmunomodulatory activities could enable an entirely new generation of therapeutic targets with the potential to treat, delay, and possibly even prevent AD and other neurodegenerative diseases.

抽象的阿尔茨海默病 (AD) 和其他神经退行性疾病是导致死亡的主要原因美国老年人的残疾率超过 650 万。作为AD 目前无法治愈或预防，迫切需要有效的治疗方法针对潜在的疾病过程。治疗开发的一个主要障碍是缺乏好的目标。尽管在病理学上很重要，但淀粉样蛋白斑块和 tau 蛋白缠结物不易药物化，针对这些蛋白质的治疗方法的临床试验直接很大程度上失败了。最近的全基因组关联研究发现了一个联系神经免疫细胞上越来越多的调节蛋白之间的关系，特别是小胶质细胞和星形胶质细胞的表面，与患 AD 的风险有关。这具有神经免疫调节活性的新蛋白质的鉴定可以使完全新一代治疗靶点具有治疗、延迟甚至可能的潜力预防 AD 和其他神经退行性疾病。