In Vivo Optical Imaging of Alpha-Synuclein Aggregation

α-突触核蛋白聚集的体内光学成像

基本信息

批准号：
9791004
负责人：
Kevin J Webb
金额：
$ 22.09万
依托单位：
PURDUE UNIVERSITY
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：
2018-09-30 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9791004
关键词：
Address Animal Model Animals Area Brain Brain Injuries Brain Stem Brain imaging Cell Culture Techniques Cell secretion Chemistry Complex Data Development Disease Disease Progression Economic Burden Evaluation Evolution Fluorescence Fluorescence Resonance Energy Transfer Genetic Goals Health Human Image In Vitro Label Light Link Maps Measurement Medical Research Medicine Methods Microscope Modeling Molecular Molecular Biology Molecular Conformation Monitor Movement Disorders Nerve Degeneration Neurodegenerative Disorders Neuronal Dysfunction Neurons Neurosciences Onset of illness Optics Parkinson Disease Pathogenesis Pathogenicity Pathway interactions Patients Performance Plant Roots Play Prevalence Proteins Rattus Research Resolution Signal Transduction Time Tissues United States Universities Validation Work alpha synuclein animal imaging base disorder risk effective therapy experimental study fluorescence imaging fluorophore health application imaging approach imaging modality imaging study in vivo in vivo imaging in vivo optical imaging insight light scattering microscopic imaging molecular imaging motor symptom nanometer neuron loss novel therapeutic intervention optical imaging presynaptic programs protein aggregate protein aggregation protein folding public health relevance success tissue phantom

项目摘要

Project Summary In Vivo Optical Imaging of Alpha-Synuclein Aggregation Kevin Webb, J. Chris Rochet, and Jason Cannon, Purdue University This project entails the application of a high resolution whole brain optical molecular imaging method to determine the pathogenic mechanism involved in the temporal and spatial development of Parkinson's disease (PD). PD is a debilitating movement disorder afﬂicting 5 million people worldwide that imposes an economic burden of more than $14 billion each year in the United States alone. While the causes of most cases are unknown, environmental and genetic factors have been repeatedly linked to increased PD risk. Abnormal aggregation of the presynaptic protein alpha-synuclein (aSyn) is thought to play a key role in PD pathogenesis. Aggregation is postulated to occur at an early stage in the brain stem, and then in later stages in speciﬁc areas of the brain where neuronal loss or dysfunction results in the cardinal motor symptoms. Although the mechanism by which aSyn aggregation migrates throughout the brain is not well understood, there is evidence that cell secretion pathways are involved. We will optically image states of aSyn aggregation throughout the whole living brain at high spatial resolution and at different times of aSyn expression, presenting a basis for achieving critically needed understanding related to PD onset and progression. The approach will use our recent discovery of a method to form images with unprecedented spatial resolution from highly scattered light and our earlier discovery of how to image ﬂuorescence resonance energy transfer (FRET) in vivo. Completion of this project will enable us to extract critical insights into the time-course and extent of aSyn propagation throughout the brain, as well as the aggregation state of transmitted aSyn species, in a live animal model. Knowing the basis for progression of PD will provide opportunities for the development of early-stage treatment, before substantial brain damage occurs.

项目摘要 α-核蛋白聚集的体内光学成像凯文·韦伯（Kevin Webb），J。ChrisRochet和Purdue University Jason Cannon 该项目实体应用高分辨率全脑光学分子成像方法来确定帕金森氏病暂时和空间发展涉及的致病机制（PD）。 PD 是一种令人衰弱的运动障碍，全世界有500万人，不可能仅在美国，每年超过140亿美元。虽然大多数情况的原因尚不清楚，但环境和遗传因素已反复与PD风险增加有关。异常聚集突触前蛋白α-突触核蛋白（ASYN）被认为在PD发病机理中起关键作用。聚合是假设是在脑干的早期阶段发生，然后在大脑的特定区域的后期神经元丧失或功能障碍导致基本运动症状。虽然是 Asyn聚集在整个大脑中迁移尚不清楚，有证据表明细胞分泌涉及途径。我们将在整个活着的大脑中光学地图像ASYN聚集的状态高空间分辨率和ASYN表达的不同时间，为实现急需的基础提供了了解与PD发作和进展有关。该方法将使用我们最近发现的方法来从高度分散的光中形成前所未有的空间分辨率的图像，以及我们早期发现如何在体内图像荧光共振能量转移（FRET）。该项目的完成将使我们能够提取对ASYN在整个大脑中传播的时刻和程度的批判性见解，以及在活动物模型中，传播Asyn物种的聚集状态。了解PD进展的基础在发生重大脑损伤之前，将为早期治疗的发展提供机会。