Modulation of Endoplasmic Reticulum Stress by Sigma Ligand

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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.