Molecular neuropathology of TDP-43 proteinopathies

TDP-43 蛋白病的分子神经病理学

基本信息

批准号：
9274104
负责人：
Edward Byung-Ha Lee
金额：
$ 20.13万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2018-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9274104
关键词：
Affect Aging Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Autopsy Behavioral Biochemical Brain Brain Pathology Cell Fractionation Cell Nucleus Cells Clinical Cytoplasm Cytoplasmic Granules Data Disease Exhibits Experimental Models Fluorescence Functional disorder Genetic Goals Heterogeneity Histopathology Human Laboratories Language Link Messenger RNA Metabolism Methods Molecular Molecular Abnormality Molecular Analysis Motor Neuron Disease Motor Neurons Nerve Degeneration Neurodegenerative Disorders Neurons Nuclear Nuclear RNA Parkinson Disease Pathogenesis Pathologic Pathology Patients Pennsylvania Physicians Population Proteins RNA RNA Binding RNA Processing RNA Sequences RNA Splicing RNA-Binding Proteins Resources Scientist Sorting - Cell Movement Spastic Stress Symptoms Syndrome Techniques Temporal Lobe Testing Time Toxic effect Universities Variant base brain research brain tissue clinical phenotype corticobasal degeneration frontal lobe frontotemporal degeneration hippocampal sclerosis innovation insight interest neuropathology neurotoxicity novel protein TDP-43 protein aggregate spasticity stressor trafficking transcriptome sequencing

项目摘要

Project Summary Amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) are two related neurodegenerative diseases which share overlapping clinical, pathologic and genetic features. The ALS-FTD spectrum of diseases is uniformly fatal, and there is neither treatment nor cure. There is a remarkable convergence of pathologic and genetic data which indicate that abnormal RNA metabolism is linked to neurodegeneration in ALS and FTD. The overall goal of this proposal is define the molecular neuropathology of ALS and FTD using human brain tissue. Understanding the molecular aberrations associated with specific brain pathologies will reveal insights into the molecular pathogenesis of ALS/FTD. Novel methods are presented in which pathologic proteins or neurons are isolated from human brain for deep molecular analysis. Two specific aims are proposed which will (1) determine the molecular composition of pathologic TDP-43 protein inclusions, and (2) identify the abnormalities in RNA processing due to the loss of normal nuclear TDP- 43 protein. These studies will further our understanding of TDP-43 proteinopathies by using highly innovative techniques to study human brain tissue with advanced molecular techniques.

项目摘要肌萎缩性侧索硬化症（ALS）和额颞变性（FTD）是两个相关的具有重叠临床，病理和遗传特征的神经退行性疾病。 als-ftd 疾病的频谱是统一的致命性，既没有治疗也没有治愈。有一个了不起的病理学和遗传数据的收敛性，表明异常RNA代谢与 ALS和FTD中的神经变性。该提议的总体目标是定义分子神经病理学使用人脑组织的ALS和FTD。了解与特定相关的分子像差脑病理学将揭示对ALS/FTD分子发病机理的见解。新方法是从人脑中分离出病理蛋白或神经元以进行深层分子分析。提出了两个具体目标，该目标将（1）确定病理TDP-43的分子组成蛋白质夹杂物，（2）由于正常核TDP- 43蛋白。这些研究将通过使用高度创新性来进一步我们对TDP-43蛋白质病的理解用晚期分子技术研究人脑组织的技术。