Modulation of Endoplasmic Reticulum Stress by Sigma Ligand

在大脑中，数十亿个神经元紧密地组装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。这种放电是至关重要的，因为这是神经元相互交流的方式。为了保持大脑健康，网络内部存在着微妙的平衡。每个神经元可以比作一个工厂，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其他大脑区域的功能。在产生如此数量的蛋白质时，有时神经元会犯错误并产生不良蛋白质。这些坏的蛋白质会干扰大脑的整体功能，也可能导致细胞死亡。为了尽量减少这些合成不良的蛋白质的影响，神经元使用一种“过滤器”。这个“过滤器”回收坏的，但让好的蛋白质离开神经元。在过去的5年里，我们的实验室一直在研究一种在大脑中大量存在的小化学物质的作用。这种化学物质被称为sigma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σ受体可以增加神经元的“过滤”能力。由于这些“过滤器”对于保持神经元的健康至关重要，因此人们可以预期，增加这些“过滤器”的功能将有利于保持大脑的健康。

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.**