Two science articles reveal the structure of key brain receptor complex, which is expected to develop a variety of new therapies for nervous system diseases

December 12, 2019 / BIOON / -- recently, in a research report published in the international journal Science, scientists from Vanderbilt University School of medicine and other institutions successfully revealed the mystery of key brain receptor complexes through research The glutamate receptor named AMPARs in the brain is very important for synaptic plasticity, learning and memory The dysfunction of AMPARs receptor is often directly related to the occurrence of a variety of neurological and mental diseases, including epilepsy, Alzheimer's disease, severe depression and autism spectrum disorders Photo source: cc0 public domain reveals that the formation mechanism and action mechanism of AMPARs are very important for the development of new pharmaceutical compounds These compounds may help improve the treatment of multiple diseases by improving or reducing the activity of AMPARs In this paper, the structure of AMPARs has been revealed for the first time, and they also carry an auxiliary subunit called cnih3; these potential drug targets have been found by researchers using frozen electron microscopy AMPARs are short for AMPA type ionotropic glutamate receptors They are a kind of ligand gated ion channels, which can be embedded in the cell membrane of nerve cells, and these nerve cells will be activated by neurotransmitter glutamate These receptors can generate signals through the charged ions flowing through them AMPARs can be regulated by a membrane protein called auxilliary subunit, which can form a complex complex with AMPARs One of the most common regulators is the protein family called Cornichon (cnih) When the specimen is frozen to preserve the structure, the frozen electron microscope can produce ultra-high resolution images In this paper, the researchers obtained the first molecular image of AMPARs cnih3 complex combined with lipid molecules based on this technology By analyzing this structure, the researchers found that the folding of cnih3 in the cell membrane is not the same as predicted by the computer algorithm, based on this structure , the researchers hypothesized that cnih3's binding site is located near the glua subunit that forms the receptor's ion pore, which may serve as a potential target to help develop new drugs to effectively control the ion channel activity of AMPARs Later researchers will further study the key brain receptor complex to develop new targeted therapies for the treatment of various nervous system diseases, including Alzheimer's disease Original source: Jochen schwenk, Bernd fakler Folding unpredicted, Science (2019) Doi: 10.1126/science.aaz8642 terunaga Nakagawa Structures of the AMPA receiver in complex with its auxiliary subunit Cornichon, Science (2019) Doi: 10.1126/science.aay2783