Enhancement of Neuronal Plasticity and Axon Regeneration Capabilities of Pro-Neur

Pro-Neur 增强神经元可塑性和轴突再生能力

基本信息

批准号：
8858646
负责人：
Rafael Perez-Ballestero
金额：
$ 10.35万
依托单位：
TEXAS A&M UNIVERSITY-KINGSVILLE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-09 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8858646
关键词：
2&apos ,3&apos -Cyclic-Nucleotide Phosphodiesterases Adult Affect American Animal Model Area Automobile Driving Axon Behavior Bibliography Binding Biochemical Biological Models Blindness Blood Brain C-terminal Cells Cellular Membrane Cyclic Nucleotides Cytoskeleton Development Economic Burden Enzymes Future Genetic Glaucoma Goals Growth Associated Protein 43 Health Health Care Costs Healthy People 2020 Homologous Gene Human Individual Intervention Investigation Journals Knowledge Laboratories Learning Life Mammals Medical Membrane Mission Modeling Modification Molecular Molecular Probes Molecular Target Myelin Sheath N-terminal Natural regeneration Nature Nerve Nerve Fibers Nerve Regeneration Neuraxis Neurites Neuroglia Neuronal Differentiation Neuronal Plasticity Neurons Organ Organism Outcome PC12 Cells Paralysed Pathology Peripheral Nervous System Play Process Protein Binding Proteins Public Health Quality of life Research Retinal Ganglion Cells Rodent Role Science Somatic Cell Spinal Cord Spinal cord injury Stem cells System Tertiary Protein Structure Testing Tissues Tubulin United States National Institutes of Health Variant Vertebrates Work Zebrafish axon growth axon regeneration base burden of illness cold blooded vertebrate combinatorial disability expression vector human disease improved innovation mutant nerve stem cell novel optic nerve regeneration organ regeneration overexpression phosphoric diester hydrolase protein function repaired stem cell differentiation success synergism targeted treatment teleost fish tool

项目摘要

DESCRIPTION (provided by applicant): Humans, as warm-blooded vertebrates, do not regenerate axons in their central nervous system (CNS) spontaneously. Conversely, cold-blooded vertebrates demonstrate remarkable abilities for nerve regeneration in their CNS. Studies of the molecular mechanisms of nerve regeneration have led to the discovery of several proteins that are induced during successful nerve regeneration. Analysis of the teleost fish optic nerve regeneration system led us to the identification of the RICH proteins. Several mutant versions of zebrafish RICH (zRICH) proteins have been generated and studied in our laboratory at the biochemical and cellular levels. This protein is a 2', 3'-cyclic nucleotide, 3'-phosphodiesterase that can bind to cellular membranes through a C-terminal membrane localization domain. Interestingly, our recent studies have shown that zRICH can bind to tubulin and enhance neuronal plasticity by promoting the formation of neurite branches. The central domain of the protein is sufficient for interaction with tubulin, but not for induction of neuritogenesis. One of the aims of this project is to learn additional details about the effects of zRICH in neuronal plasticity. Additional mutant versions of zRICH will be studied with our PC12 differentiation model, to learn whether the membrane localization domain or the acidic N-terminal domain play roles in neuritogenesis. A second aim is to explore the possibility of synergism of zRICH with other neuronal plasticity enhancing proteins such as GAP43 and CAP23. A third goal is exploring whether the plasticity enhancing effects can be applied to neural stem cells. The studies are relevant to public health by providing a better understanding of the process of nerve regeneration, and novel tools for the treatment of human diseases caused by damage to nerve fibers in the CNS, for example spinal cord injury.

描述（由申请人提供）：人类，作为温血脊椎动物，不会自发地在其中枢神经系统（CNS）中再生轴突。相反，冷血脊椎动物在中枢神经系统中表现出显着的神经再生能力。对神经再生的分子机制的研究导致发现了在成功再生过程中诱导的几种蛋白质。对硬骨鱼视神经再生系统的分析导致我们鉴定了富蛋白。在我们的生化和细胞水平上，已经在我们的实验室中生成并研究了几种突变版的斑马鱼蛋白（Zrich）蛋白。该蛋白是一个2'，3'-环状核苷酸，3'-磷酸二酯酶，可以通过C末端膜定位结构域与细胞膜结合。有趣的是，我们最近的研究表明，Zrich可以通过促进神经突的形成来与微管蛋白结合并增强神经元可塑性。该蛋白质的主要结构域足以与微管蛋白相互作用，但不足以诱导神经发生。该项目的目的之一是学习有关影响的其他详细信息 Zrich在神经元可塑性中。将使用我们的PC12分化模型研究Zrich的其他突变版本，以了解膜定位域或酸性N末端结构域在神经发生中起着作用。第二个目的是探索Zrich与其他神经元可塑性增强蛋白（例如GAP43和CAP23）的协同作用的可能性。第三个目标是探索是否可以将可塑性增强作用应用于神经干细胞。这些研究与公共卫生有关，通过更好地了解神经再生过程，以及通过中枢神经系统中神经纤维损害引起的人类疾病的新工具，例如脊髓损伤。