My scientist reveals the molecular mechanism of ketamine's rapid antidepressant
Provide an important theoretical basis for the design of new antidepressant research and development
Author: Our reporter Yan Weiqi
【Technological frontier】
Our newspaper, Shanghai, July 28 (Reporter Yan Weiqi) On the evening of July 28, the journal Nature published an online research paper titled "Structural Basis of Ketamine Acting on Human NMDA Receptors".
This study clearly reveals the molecular mechanism of the rapid antidepressant effect of ketamine, and provides an important theoretical basis for the design of new antidepressants, especially the promotion of the development of ketamine-derived drugs, and brings new dawn to patients with depression.
Depression is one of the most common mental illnesses.
Statistics show that nearly 300 million people of different ages worldwide suffer from depression, but for a long time, there has been a lack of fast and efficient drugs for the treatment of depression.
In 2019, ketamine was put into clinical use as a new type of antidepressant, which is the most important discovery in the antidepressant field in recent decades.
A sub-anaesthetic dose of the drug can significantly improve symptoms such as depression and even reduce suicidal ideation within a few hours, especially for treatment-resistant depression.
However, side effects such as dissociative hallucinations and addictions that coexist with this cannot be ignored either.
As a result, the development of new antidepressants with fewer side effects and quick-acting effects has become the direction of many scientists around the world.
"Depression is not a mental illness. It is not that many people think that the heart is fragile. It is that the patient's brain has changed and the synapses of the brain are damaged." According to Zhu Shujia, a researcher from the Chinese Academy of Sciences' Center for Excellence in Brain Science and Intelligent Technology Has long been engaged in a series of studies on the structure and function of NMDA receptors.
This is a class of excitatory glutamate receptors that can regulate the plasticity of brain synapses.
Studies have shown that NMDA receptor dysfunction is closely related to neurological diseases. Ketamine can participate in the regulation of synaptic transmission and synaptic plasticity signaling pathways by inhibiting the activity of NMDA receptor channels, thereby restoring the cortex and hippocampus caused by chronic stress. Synapse damage.
Zhu Shujia, born in 1984, has been engaged in NMDA receptor research for more than ten years. Two years ago, he focused his attention on the molecular mechanism of ketamine binding to NMDA receptor.
"The key to conquering diseases lies in the exploration of basic biological mechanisms." She believes that depression can be cured and requires precise intervention by various medical methods such as drugs, physics, and psychology.
In this study, the binding site of ketamine on the NMDA receptor was “seeed” and confirmed through cryo-electron microscope, and the molecular basis of the binding of ketamine to NMDA receptor was further clarified through electrophysiological function experiments and molecular dynamics simulations. Hope to promote the clinical treatment of related diseases.
"This meticulous and interesting study solves an important and timely problem in the structural biology of NMDA receptors." Experts in this field at home and abroad highly recognized this. "Considering the potential of ketamine as a new antidepressant drug in clinical applications, This research is very timely and provides important information for understanding clinically known patient mutations that alter the binding characteristics of ketamine."
Academician Zhang Mingjie, a structural biologist, believes that this breakthrough work has extremely important scientific significance and clinical value, and is expected to lead to a better clinical performance of the drug combination for the treatment of depression.
The research was completed by the Zhu Shujia research group of the Chinese Academy of Sciences Brain Science and Intelligent Technology Excellence Innovation Center (Institute of Neuroscience), the State Key Laboratory of Neuroscience, the Shanghai Brain Science and Brain-like Research Center, and the Luo Cheng research group of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences .