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Mapping Of First Neuroreceptor Expected To Revolutionize Drug Development For Neurological Diseases

 

Scientists at the University of Southern California (USC) and the Mayo Clinic College of Medicine just achieved a scientific breakthrough that has the potential to revolutionize the design of neurological drugs: they captured the first high resolution images of the acetylcholine receptor (AChR), the α7 molecule responsible for transmitting signals between neurons, particularly those associated with learning and memory.

 

Overall structures of the α7–AChBP chimera and comparison to related structures.: image via nature.comOverall structures of the α7–AChBP chimera and comparison to related structures.: image via nature.com

 

The α7 images, which have been 30 years and many failed attempts in coming, were taken from several different perspectives, allowing thorough study of these molecules as they receive and transmit neuronal signals. The α7 cannot be studied naturally, so the researchers had to build models, or chimeras, of the molecules that reacted to stimuli in the same way as they do in nature. 

Once the α7 chimeras were modelled, they had to attach to crystals so that they could be seen in high resolution - a task that was painstaking, because the α7 molecules are very flexible and don't bind easily to a fixed form.  Shu-xing Li, a postdoctoral fellow in Chen's lab, estimated that for every 100 crystals, only one or two could collect enough data that was useful.

But Chen said the effort was worth it because of   "... the rich information we can get from these crystals about human neuronal receptors, and the potential impact on drug development that can benefit human health..."

The drugs used to treat Alzheimer's, Parkinson's, schizophrenia and other neurological diseases are currently developed using a trial and error approach; scientists create a drug and then test it to see its effects on animals or human subjects. This expensive and time consuming method was necessitated because, until now, they were not able to visualize the neuroreceptors responsible for transmitting signals between neurons.

With the ability to see the impact of drugs directly on the neuroreceptors, pharmacologists will be able to quickly discern the effective drugs, and only those will go to animal or human trials. 

 

sources: MachinesLikeUs, Nature Neuroscience