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An explanatory image showing the pathway of cholesterol from the membrane into the discovered binding site on the neurotransmitter receptor. Source:IMIM.

Researchers of GRIB show that cholesterol is fundamental for signal transmission in the human brain

A study lead by researchers from the GPCR Drug Discovery Group of GRIB and the Centre for Cellular and Molecular Biology of the Council Of Scientific And Industrial Research (CSIR) published in the Science Advances journal, shows for the first time how cholesterol can interfere with the function of a important receptor present in brain cells - the serotonin receptor. This finding is of great importance, as it allows to devise new ways to modulate those receptors, which in the future could lead to the development of new drugs to treat diseases of the central nervous system.

Cholesterol is an essential component of the neuron membrane. Multiple proteins reside within those membranes, including GPCRs (G-protein coupled receptors). GPCRs are a large receptor family, encompassing serotonin receptors, which act as cellular receptors, detecting outside signals and transmitting towards the cell. Because of this, GPCRs are crucial for correct communications between cells. Those receptors are involved in the most important physiological processes, for example allowing us to perceive sensory stimuli, like vision, taste or smell. Furthermore, they play an important part in immunological events, the modulation of behavior, as well as other crucial processes in the human body.

In this study, researchers demonstrate, for the first time, how cholesterol influences the function of serotonin receptors at an atomic scale. This finding describes the structural basis of a yet undescribed cross-talk between those receptors and the membrane. "Until know it was not clear how the presence of cholesterol influences the behavior of those proteins, due to the lack of methods that can capture the dynamics of such biological events at an atomic scale" explains Dr Jana Selent, the head of the GPCR Drug Discovery Group, and the co-supervisor of the study. "The results of our study show the intimate relation between cholesterol and GPCRs of the central nervous system and highlight the key role of this molecule in signal transmission within the brain" she adds. "Our findings pave the path for novel lines of investigation, like the use of membrane components as tools to treat disorders of the central nervous system"

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The C. elegans brain with all neurons expressing green fluorescent protein (GFP), and a subset of neurons involved in feeding expressing a magenta nuclear marker. Scale bar is 10 microns. (Seth Taylor)

Research Snapshot: First-ever gene expression map of an entire nervous system completed

Extracted from Research news of Vanderbilt University website

Professors Seth Taylor and David Miller, both in Vanderbilt University's Department of Cell and Developmental Biology, along with biologists from ​Col​umbia University​, Yale University ​and IMIM ​have established a gene expression atlas for the nervous system of the nematode C. elegans. Gabriel Santpere, head of the Neurogenomics research group of GRIB has collaborated on this work. 

Their data complement the known wiring diagram of the C. elegans nervous system to create, for the first time, a complete picture of gene expression for every neuron in an entire nervous system.

The article "Molecular topography of an entire nervous system" was published online in the journal Cell on July 7.

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RISK assessment of chemicals integrating HUman centric Next generation Testing strategies promoting the 3Rs, RISK-HUNT3R, is the new European effort to develop a new modular framework for animal-free next generation risk assessment (NGRA) driven by world-leading experts from various disciplines. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 964537 for the period 2021 till 2026.

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