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publicado em 12/09/2011 às 19h15:00
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USC scientists produce the first detailed map of the human neuroreceptor

Research could pave the way for the development of better drugs to achieve neurodegenerative diseases

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For the first time, scientists have mapped a neuroreceptor USC. This scientific breakthrough promises to revolutionize the science of drugs used to treat diseases like Alzheimer's and schizophrenia.

The team was the first to produce high-resolution images of the a7 receptor (Alpha 7), a molecule responsible for transmitting signals between neurons - particularly in the brain region believed to be associated with learning and memory.

Using the image, scientists will be better equipped to design products specifically for pharmacists to interact with the receptor, rather than using an approach of trial and error. "A lot of interest in this work will come from pharmaceutical companies. They really have no clear view of it. They do not know how or why [the drugs] work," said Lin Chen the author, and professor of biological sciences and chemistry at USC College of Dornsife Letters, Arts and Sciences.

The high-resolution imaging will also help researchers in neuroscience to study how these receptors receive and transmit neural signals, a question that has puzzled researchers for decades.

The article, co-authored with scientists from the Keck School of Medicine of USC School and Mayo Clinic College of Medicine, appears in Nature Neuroscience this month.

The findings in March following the completion of Chen, decipher the inner workings of a nicotine receptor in 2007.

The d evelopment of an image receptor A7 was not a simple task, which is part of why he adopted so far to achieve this goal, despite the great interest in understanding the structure of the receiver. Trying to decipher neuroreceptors has been ongoing for 30 years. "This has been a longstanding challenge. The challenge is twofold. It is difficult to obtain enough receptor protein for structural analysis as well as the flexible nature of these receptors makes them difficult to crystallize - a necessary step for high-resolution images," said Chen.

The usual method of the biologist to study these molecules - the cultivation of a large amount using molecular cloning - failed to produce enough of the correct structure of the A7 to study. "You can not study it directly in its natural form, which is why build it," said Chen.

In the case of A7, the developer of Chen, Dr. Steve Sine, Mayo Clinic, built a molecule that shares about 70 percent of the common structure of the A7 which responded to stimuli in the same way that makes the A7 natural.

The next step was to form protein crystals with these high-resolution study. This turns out to be particularly difficult for neuronal receptors, because they are inherently flexible - they need to connect to a neurotransmitter, a small molecule that acts as a messenger in the nervous system, and transmit the signal throughout the body protein. In addition, these receptors are adorned with sugar molecules that add more flexibility to the system.

The crystallization of A7 was a painstaking process conducted by Li Shu-xing, the first author of the study and a postdoctoral fellow in the laboratory of Chen. For every one hundred crystals obtained, only one or two were good enough for structural analysis. Li had to classify hundreds of crystals to collect enough data to structural analysis. "In a sense, these crystals are probably among the world's most expensive crystals, certainly more expensive than diamond. But considering the wealth of information that can get from these crystals on the neuronal receptors of the human being, the potential impact on drug development may benefit human health, worth the effort, "said Chen.

   Palavras-chave:   Map    Neuroreceptor    Development    Drugs    Diseases and neurodegenerative diseases    Medications    California    USA   
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