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Molecular Mechanism of Neuronal Damage in Demyelinating Disorders

脱髓鞘疾病神经元损伤的分子机制

基本信息

批准号：
8645765
负责人：
Patrizia Casaccia
金额：
$ 36.46万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8645765
关键词：
Acetylation Acute Address Amino Acids Area Axon Axonal Transport Binding Brain Calcium Cells Clinical Collaborations Cuprizone Cytosol Deacetylation Demyelinating Diseases Demyelinations Detection Disease Early Diagnosis Enzymes Event Family member Fiber Glutamates Grant HDAC1 gene Hippocampus (Brain)Histone Deacetylase Histones Impairment In Vitro Knock-in Mouse Knowledge Laboratories Lead Mitochondria Modification Molecular Movement Multiple Sclerosis Mus Mutation Nerve Degeneration Neurites Neurodegenerative Disorders Neurons Nuclear Nuclear Export Nuclear Receptors Oxidative Stress Pathway interactions Patients Phosphorylation Point Mutation Post-Translational Protein Processing Property Protein Isoforms Proteins Recycling Reporting Role Signal Transduction Slice Specificity Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stimulus Swelling Synaptic Vesicles TNF gene Testing Therapeutic Toxic effect Transgenic Model Transport Vesicles Ubiquitination axonopathy base cell type disability immunoreactivity in vivo in vivo Model inhibitor/antagonist mutant nervous system disorder new therapeutic target novel prevent protective effect public health relevance repaired research study response young adult

项目摘要

DESCRIPTION (provided by applicant): Axonal damage is cause of major clinical disability in a wide range of neurological disorders, including multiple sclerosis (MS). Although considerable progress has been made in the detection of the early signs of axonal damage, still very little is known about the potential causative factors and the related signaling events. Thus, therapeutic approaches aimed at preventing or repairing damaged axons are not yet available. Our laboratory has recently reported the involvement of cytoplasmic HDAC1 in the impairment of mitochondrial transport and the onset of axonal swellings. This experimental plan proposes to characterize this novel intracellular signaling mechanism and use in vitro and in vivo models to characterize the role of specific isoforms of histone deacetylases in axonal damage in demyelinating disorders.

描述（由申请人提供）：轴突损伤是多种神经系统疾病（包括多发性硬化症（MS））中主要临床残疾的原因。尽管在检测轴突损伤的早期迹象方面已经取得了相当大的进展，但对于潜在的致病因素和相关信号事件仍然知之甚少。因此，目前还没有旨在预防或修复受损轴突的治疗方法。我们的实验室最近报道了细胞质 HDAC1 参与线粒体运输受损和轴突肿胀的发生。该实验计划旨在表征这种新颖的细胞内信号传导机制，并使用体外和体内模型来表征组蛋白脱乙酰酶的特定亚型在脱髓鞘疾病的轴突损伤中的作用。