Sphingolipid Biology of Neurodegeneration

神经变性的鞘脂生物学

• 批准号: 8349852
• 负责人: Richard Proia
• 金额: $ 48.58万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349852
• 关键词: Address; Biology; Catabolism; Cell membrane; Clinical; Complex; Defect; Disease; Family; Future; Genes; Gliosis; Goals; Inflammation; Inherited; Longevity; Membrane; Membrane Lipids; Modeling; Mus; Nerve Degeneration; Nervous system structure; Neurodegenerative Disorders; Process; Production; Role; Sandhoff Disease; Signal Transduction; Sphingolipids; Sphingosine-1-Phosphate Receptor; improved; mouse model; neuron apoptosis; research study; sphingosine 1-phosphate; sphingosine kinase

We have determined that the sphingosine kinase/S1P receptor axis has a significant role during neurodegeneration. We used a well-established Sandhoff mouse model of neurodegeneration, which included neuronal apoptosis, inflammation and gliosis. In order to determine if S1P production was important during the neurodegenerative process we deleted the Sphk1 gene in the Sandhoff model. We found a significant improvement in life span and clinical condition of these mice compared with the control Sandhoff mice with a normal Sphk1 gene. These results indicate that Sphk1 expression may have contributed to the neurodegenerative course. Future experiments will address the mechanism of the improved course of the disease.

我们已经确定鞘氨酸激酶/S1P受体轴在神经变性中起重要作用。我们使用了一个完善的Sandhoff小鼠神经变性模型，包括神经元凋亡，炎症和胶质瘤。为了确定S1P的产生在神经退行性过程中是否重要，我们在Sandhoff模型中删除了Sphk1基因。我们发现，与正常Sphk1基因的Sandhoff小鼠相比，这些小鼠的寿命和临床状况有显著改善。这些结果表明Sphk1的表达可能与神经退行性过程有关。未来的实验将探讨疾病改善过程的机制。