Modulation of Endoplasmic Reticulum Stress by Sigma Ligand

Sigma 配体对内质网应激的调节

• 批准号: RGPIN-2015-05572
• 负责人: Bergeron, Richard
• 金额: $ 1.75万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590512
• 关键词: Modulation; Endoplasmic; Reticulum; Stress; Sigma

In the brain, billions of neurons are tightly assembled in a complicated network. Altogether, like musicians in an orchestra, they fire in synchrony. This firing is crucial since that's the way neurons communicate with one another. To keep the brain in good health, there exist a delicate balance within the network. Each neuron can be compared to a factory, making thousands and thousands of proteins every day. Each of these proteins could affect the functioning of other brain areas. In producing such amount of proteins, sometimes, the neurons make mistakes and produce bad proteins. These bad proteins could disturb the overall function of the brain and may also induce cell death. In order to minimize the impact of these badly synthesized proteins, the neurons use a kind of “filter”. This “filter” recycle the bad and but let go the good proteins outside the neurons. In the last 5 years, our lab has been investigating the role of a small chemical that is found in the brain in huge quantity. This chemical is called sigma receptor. What is unique about the sigma receptor is the fact that it can enhance the “filter” capacity of each neuron. Indeed, our preliminary data demonstrate that stimulating sigma receptor with selective compounds can increase the “filter” capacity of the neurons. Since these “filters” are absolutely crucial for keeping neurons in good health, one would expect that increasing the function of these “filters” will be beneficial to maintain good health of the brain.

在大脑中，数十亿个神经元紧密地聚集在一个复杂的网络中。总而言之，就像管弦乐队中的音乐家一样，他们同步开火。这种激发是至关重要的，因为这是神经元相互交流的方式。为了保持大脑的健康，网络内部存在着微妙的平衡。每个神经元都可以比作一座工厂，每天制造成千上万的蛋白质。这些蛋白质中的每一种都可能影响大脑其他区域的功能。在产生如此大量的蛋白质时，有时神经元会犯错误，产生不好的蛋白质。这些不良蛋白质可能会扰乱大脑的整体功能，还可能导致细胞死亡。为了将这些合成不佳的蛋白质的影响降到最低，神经元使用了一种“过滤器”。这种“过滤器”回收坏的蛋白质，但把好的蛋白质从神经元外释放出去。在过去的5年里，我们的实验室一直在研究一种在大脑中发现的大量小型化学物质的作用。这种化学物质被称为西格玛受体。Sigma受体的独特之处在于，它可以增强每个神经元的“过滤”能力。事实上，我们的初步数据表明，用选择性化合物刺激sigma受体可以增加神经元的“过滤”能力。由于这些“过滤器”对保持神经元的健康是绝对关键的，人们可以预料，增加这些“过滤器”的功能将有益于保持大脑的良好健康。