RNA Dysregulation in ALS

ALS 中的 RNA 失调

基本信息

批准号：
7942819
负责人：
ROBERT B DARNELL
金额：
$ 49.76万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7942819
关键词：
Address Affect Aliquot American Amyotrophic Lateral Sclerosis Animals Autopsy Binding Sites Clinical Collection Complement Data Defect Development Diagnostic Disadvantaged Disease Exons Familial Amyotrophic Lateral Sclerosis Functional disorder Generations Genetic Variation Human Human Genetics Individual Intervention Laboratories Maps Mediating Methods MicroRNAs Modeling Motor Motor Neurons Mus Mutate Mutation Neocortex Neurons Pathogenesis Pathway interactions Patients Play RNA RNA Binding RNA Sequences RNA analysis RNA-Binding Proteins RNA-Protein Interaction Regulatory Pathway Role Sampling Site Techniques Technology Tissues Variant Work disease diagnosis genome wide association study genome-wide human tissue insight interest mouse model nervous system disorder next generation protein TDP-43 public health relevance research study stem therapeutic target

项目摘要

DESCRIPTION (provided by applicant): This is a proposal to explore the role of RNA dysregulation in the pathogenesis of amyotrophic lateral sclerosis (ALS). The work stems from recent findings that rare patients with familial ALS have mutations in RNA binding proteins. We will use newly developed methods to look at normal and abnormal RNA-protein interactions in tissues obtained from mouse models of ALS and from human ALS samples obtained at autopsy. This work has the potential to uncover new insights, as well as diagnostic markers and therapeutic targets for ALS. In addition, the use of new methods and paradigms will serve as a model for how to approach a growing list of neurologic disorders associated with RNA dysregulation. PUBLIC HEALTH RELEVANCE: This work is a study of a currently fatal human neurologic disorder that currently affects over 20,000 Americans. There is no means of diagnosing the disease short of clinical examination, and there is no treatment. The work offers the hope of understanding the cause, and of developing diagnostic markers and therapeutic targets for the disorder.

描述（由申请人提供）：这是探索RNA失调在肌萎缩性侧面硬化症（ALS）发病机理中的作用的建议。这项工作源于最近的发现，罕见的家族性ALS患者在RNA结合蛋白中具有突变。我们将使用新开发的方法来查看从ALS小鼠模型以及从尸检时获得的人类ALS样品获得的组织中的正常和异常的RNA-蛋白相互作用。这项工作有可能发现新的见解，以及ALS的诊断标记和治疗靶标。此外，使用新方法和范例将作为如何处理与RNA失调相关的越来越多的神经系统疾病列表的模型。公共卫生相关性：这项工作是对当前致命的人类神经系统疾病的研究，目前影响了20,000多名美国人。没有临床检查缺乏疾病的手段，也没有治疗。这项工作提供了理解原因的希望，并为该疾病开发了诊断标记和治疗靶标。