Role of Heparin Sulfate in Neuregulin Signaling during Development and in Disease

硫酸肝素在发育和疾病过程中神经调节蛋白信号传导中的作用

• 批准号: 7277823
• 负责人: MARK S. PANKONIN
• 金额: $ 3.83万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277823
• 关键词: Affect; Animal Model; Animals; Axon; Cells; Cerebrum; Chemicals; Childhood; Clinical; Data; Demyelinating Diseases; Deterioration; Development; Disease; Etiology; Event; Grant; Heparin; Histological Techniques; Histopathology; Human; Image; Immunohistochemistry; Impaired cognition; Individual; Inflammation; Injury; Inorganic Sulfates; Lead; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediating; Missense Mutation; Modeling; Mouse Strains; Mutation; Myelin; Myelin Proteolipid Protein; N-acetylaspartate; Nervous System Physiology; Neuregulins; Neurological status; Pathogenesis; Patients; Pelizaeus-Merzbacher Disease; Physiology; Point Mutation; Proteins; Proteolipids; Quadriplegia; Range; Rodent; Rodent Model; Role; Severities; Severity of illness; Signal Transduction; Spastic Paraparesis; Spectrum Analysis; Syndrome; Tertiary Protein Structure; Testing; Time; Unspecified or Sulfate Ion Sulfates; brain tissue; dysmyelination; light microscopy; novel therapeutics; null mutation

Axonal loss is an important cause of clinical deficits in patients with MS. Because the etiology of MS is not known, it is impossible to be certain of the precise sequence of events that leads to axonal injury in the disease. The study of another myelin related disorder Pelizaeus- Merzbacher disease (PMD), a disease with a known cause, i.e. mutations affecting the major CNS myelin protein proteolipid protein (PLP1) may provide a better understanding of alternative (to inflammation) disease mechanisms in PMD, which may also be important in MS. Magnetic resonance spectroscopy (MRS), and imaging (MRI), as well as various histological techniques will be utilized to identify the critical domains of this protein that mediate its axon maintaining function in an attempt to better understand the pathogenesis and temporal progression of PMD. Hopefully these findings will provide a model for the clinical deterioration found in PMD as well as MS, and perhaps lead to new therapeutic approaches.

轴突丢失是MS患者临床缺陷的重要原因。由于MS的病因尚不清楚，因此不可能确定导致疾病中轴突损伤的事件的确切顺序。对另一种髓鞘相关疾病Pelizaeus- Merzbacher病（PMD）的研究可能会更好地了解替代疗法，PMD是一种病因已知的疾病，即影响主要CNS髓鞘蛋白质蛋白脂质蛋白（PLP 1）的突变。（炎症）PMD中的疾病机制，这在MS中也可能是重要的。磁共振波谱（MRS）和成像（MRI），以及各种组织学技术将被用来确定这种蛋白质的关键结构域，介导其轴突维持功能，试图更好地理解PMD的发病机制和时间进展。希望这些发现将为PMD和MS的临床恶化提供一个模型，并可能导致新的治疗方法。