Control of neuroprotection through NMDA receptor-dependent regulation of antioxidant status.

通过 NMDA 受体依赖性抗氧化状态调节来控制神经保护。

• 批准号: G0902044/1
• 负责人: Giles Hardingham
• 金额: $ 245.69万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0902044%2F1
• 关键词: Control; neuroprotection; through; NMDA; receptor

Nerve cells (neurons) communicate by releasing chemical messengers onto each other, which are detected by specialised receptors. Low-level activation of an important receptor, the NMDA receptor (NMDAR), causes activation of signals that improve a neuron‘s chance of survival. We aim to understand the exact nature of these signals. Understanding the brain‘s natural neuroprotective mechanisms is important, since malfunction of these mechanisms may contribute to neurodegeneration in certain debilitating disorders (e.g.Alzheimer‘s, ALS, Parkinson‘s), and also neurodevelopmental disorders associated with too little NMDAR activity (e.g.Foetal Alcohol Syndrome). In contrast to the beneficial effects of modest NMDAR activity, too much NMDAR activation can kill neurons. This can occur when the brain is starved of blood supply, as happens in a stroke, and can even happen in certain neurodegenerative diseases. However, these disorders cannot be treated by blocking the NMDAR with drugs, since this is harmful too. We will investigate how blocking downstream consequences of NMDAR overactivation, rather than the NMDAR itself, can protect neurons in models of disease and injury, possibly leading to therapeutic targets for stroke or novel treatments. Our investigations will include studies on stem cell-derived human neurons, a theoretically limitless source of neurons with potentially increased relevance to human disease.

神经细胞（神经元）通过相互释放化学信使进行交流，这些化学信使可以被专门的受体检测到。重要受体 NMDA 受体 (NMDAR) 的低水平激活会导致信号激活，从而提高神经元的生存机会。我们的目标是了解这些信号的确切性质。了解大脑的天然神经保护机制非常重要，因为这些机制的故障可能会导致某些衰弱性疾病（例如阿尔茨海默氏症、ALS、帕金森氏症）的神经退行性变，以及与 NMDAR 活性过低相关的神经发育障碍（例如胎儿酒精综合症）。与适度 NMDAR 活性的有益效果相反，过多的 NMDAR 激活会杀死神经元。当大脑缺乏血液供应时（如中风），甚至某些神经退行性疾病也会发生这种情况。然而，这些疾病不能通过药物阻断 NMDAR 来治疗，因为这也是有害的。我们将研究如何阻断 NMDAR 过度激活的下游后果，而不是 NMDAR 本身，可以保护疾病和损伤模型中的神经元，从而可能导致中风或新疗法的治疗靶点。我们的研究将包括对干细胞衍生的人类神经元的研究，理论上，神经元是无限的来源，与人类疾病的相关性可能会增加。