A group of Spanish researchers has managed to establish new findings regarding the behavior of cholesterol in the body. The results of the study are encouraging and open up a possible avenue for treatment around this substance.

This new study has been developed by researchers from the University of Barcelona and the August Pi i Sunyer Biomedical Research Institute (Idibaps).

Specifically, they have managed to identify a new mechanism involved in the movement of cholesterol inside the cells; which “could become a therapeutic target” against pathologies caused by dysfunctions in intracellular cholesterol transport.

A new finding on cholesterol

The research carried out by Spanish researchers has been published in the prestigious journal 'Journal of Cell Biology

'. This analysis demonstrates how the protein SNX13 plays a fundamental role in the process of transporting cholesterol out of the organelles in charge of cellular digestion, lysosomes.

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In this sense, it is necessary to clarify that the main purpose of this research work was to analyze the mechanism by which cholesterol leaves the lysosomes, a common process that requires a coordinated action between transporters NPC1 and NPC2 which, together with the lysosomal lipid bis(monoacylglycerol)phosphate, “mobilize and export free cholesterol”.

In this regard, this group of researchers recalls that the vast majority of the cholesterol used by cells comes from outside, and it is from there that they reach the lysosomes to later be distributed throughout the different molecular compartments of the organism.

Researchers speak of a “future therapeutic target”

The magnitude of this research has led to the fact that, after obtaining the results, the researchers talk about the fact that this finding could give rise to a therapeutic target for Niemann-Pick type C disease, which currently has no cure.

This pathology is caused by mutations in the transport of lysosomal cholesterol NPC1 and NPC2, which prevents the normal metabolism of cholesterol and other fats. In addition, it causes significant negative effects on the brain, liver and spleen.

The first author of the study, Albert Lu, points out that “our genetic screens identified a high number of genes involved in the metabolic regulation of cholesterol and BMP (Bone Morphogenetic Protein), whose role was not known in this context” .

Likewise, Lu has detailed the close relationship and regulation between the levels of these two lipids, which have been confirmed with the research that concerns us.

«In the absence of NPC1 function, the reduction of the SNX13 protein caused a redistribution of lysosomal cholesterol towards the plasma membrane”, argues Albert Lu.

On the other hand, the researchers confess that the results of this study provide an unexpected view regarding the regulation of these lipids. When referring to an unexpected vision, they clarify that it is due to the fact that there are few alternative mechanisms in this regard that allow the exit of cholesterol when the NPC1 transporter is inhibited or mutated.

In conclusion, the co-author of this research work, Carles Enrich, argues that “they recently described an alternative regulated by annexin-A6, and with this new work they provide new evidence that there may be alternative exit routes of lysosomal cholesterol parallel to that of NPC1”.

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