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.

项目概要 α-突触核蛋白聚集的体内光学成像 Kevin Webb、J. Chris Rochet 和 Jason Cannon，普渡大学该项目需要应用高分辨率全脑光学分子成像方法来确定帕金森病（PD）时空发展的致病机制。是一种使人衰弱的运动障碍，困扰着全世界 500 万人，造成了仅在美国，每年的损失就超过 140 亿美元，尽管大多数病例的原因尚不清楚，环境和遗传因素反复与 PD 风险增加相关。突触前蛋白 α-突触核蛋白 (aSyn) 被认为在 PD 发病机制中发挥着关键作用。假设发生在脑干的早期阶段，然后在大脑的特定区域发生神经元丢失或功能障碍导致主要运动症状的机制。 aSyn 聚集在整个大脑中的迁移尚不清楚，有证据表明细胞分泌我们将对整个活体大脑中 aSyn 聚集的状态进行光学成像。高空间分辨率和不同时间的 aSyn 表达，为实现迫切需要的目标提供了基础该方法将使用我们最近发现的一种方法来了解与 PD 发病和进展相关的知识。利用高度散射的光形成具有前所未有的空间分辨率的图像，以及我们早期发现的如何该项目的完成将使我们能够对体内荧光共振能量转移（FRET）进行成像。提取对 aSyn 在整个大脑中传播的时间过程和程度的重要见解，以及在活体动物模型中传播的 aSyn 物种的聚集状态了解 PD 进展的基础。将为在严重脑损伤发生之前进行早期治疗提供机会。