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: 6772547
• 负责人: MARK S. PANKONIN
• 金额: $ 3.41万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6772547
• 关键词: aspartate; axon; clinical research; disease /disorder model; gene expression; histopathology; human subject; immunocytochemistry; laboratory mouse; leukodystrophy; light microscopy; magnetic resonance imaging; molecular pathology; myelin; myelin proteolipid; myelinopathy; neural degeneration; neurophysiology; nuclear magnetic resonance spectroscopy; pathologic process; point mutation; tissue /cell culture

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.

轴突丧失是多发性硬化症患者临床缺陷的一个重要原因，由于多发性硬化症的病因尚不清楚，因此不可能确定导致该疾病轴突损伤的事件的精确顺序。另一种髓鞘相关疾病Pelizaeus- Merzbacher病（PMD）的研究，是一种已知病因的疾病，即影响主要中枢神经系统髓鞘蛋白蛋白脂质蛋白（PLP1）的突变，可以更好地了解PMD的替代（炎症）疾病机制，这在ms中也很重要。为了更好地了解PMD的发病机制和时间进展，我们将利用各种组织学技术来鉴定该蛋白介导其轴突维持功能的关键结构域。希望这些发现能够为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。