The Gamma-Secretase regulates the metabolism of fat in the brain
As a starting point for the treatment of Alzheimer’s disease and cancer, the so-called Gamma will be investigated-Secretase has for some time already. A new study shows how Gamma-Secretase affects the metabolism of fat in the cells and provides important insights on this particular mechanism.
Researchers from the University of Bonn have studied the influence of Gamma-Secretase on the cellular metabolism of fat, and found that here is a possible starting point could be for future cancer therapies. The hopes for new approaches against Alzheimer’s disease were, however, disappointed rather. The results of the study were published in the English journal “Life Science Alliance”.
What is the role of the plasma membrane?
Every cell in the body is surrounded by a film of grease-like cuticle, the so-called plasma membrane. This also contains numerous proteins, which act on the membrane from outside to inside span and as Sensors for the cell. When these proteins meet certain molecules on the outside, generate on the inner side of the membrane a Signal and regulate certain reactions within the cell. Other membrane proteins are able to transport certain substances into the cell.
Important function of the Gamma-Secretase
The Gamma-Secretase carries out important functions in the release of membrane-anchored signaling proteins. The Gamma-Secretase discarded membrane proteins dismembered, for example, in single parts, which are then disposed of. This is the function of the Secretase has been used for two decades, is particularly interesting for the study of Alzheimer’s disease.
Zerstück of the APP Protein appears Alzheimer’s to promote
Many brain cells contain in their membrane a Protein called APP. If the Gamma-Secretase APP dismembered into smaller parts, is one of the fragments lodged in the brain fluid. This is the so-called Abeta-peptide. This is the main component of the Plaques found in the destroyed areas of the brain of Alzheimer’s patients. “Originally, it was hoped, therefore, that inhibition of Gamma-Secretase Alzheimer’s disease, brakes,” explains Prof. Dr. Jochen Walter from the University of Bonn, in a press release. This is not working yet.
What happens in the event of failure of the Gamma-Secretase?
If the Gamma-fails Secretase, this leads to the fact that the membrane trashy one after the other. Thus, for example, certain molecules can be not so good in the cell is introduced, which leads to serious consequences, in which APP plays a key role, report the researchers.
Inhibited Gamma-Secretase has fatal consequences
The Gamma-Secretase is inhibited in cell cultures, collects APP in the membranes, which impedes the uptake of lipoproteins from the environment. This mechanism sets a fatal process in motion. So-called lipoproteins are particles made of proteins and fat-like molecules, the lipids. If there is too little lipids in the cells, the cells that have a lipid deficiency in the product, to increase its remediation, the cell’s own Lipid synthesis is.
As fat accumulates in cells
In the case of inhibition of Secretase, a Central Regulator of Lipid activates the synthesis of labeled LXR strong. Lipids are then transported partially out of the cell, due to the impaired Lipoprotein uptake by the cell, but receives no Feedback about the findings of a successful measure. Therefore, more lipids are produced, which leads to droplets of an accumulation of fat. This contributes to a fatty degeneration in the cell interior, which is also important cellular functions can be disturbed.
The disturbance of lipid metabolism leads to Alzheimer’s?
“Other studies have already shown that a disturbance of lipid metabolism in the brain may also contribute to the development of Alzheimer’s disease”, says Professor Walter. The current investigation provide clues to what mechanism this can be done. The inhibition of Gamma-Secretase can cause perhaps exactly the opposite effect that it is hoped by this measure, adds the expert.
Inhibition of Gamma-Secretase for the treatment of cancer
The inhibition of Gamma-Secretase is a promise, the researchers reported, however, success for the treatment of cancer. There are in the cell membrane proteins, which stimulate the cell division. Is switched off in tumor cells, the Gamma-Secretase, will not be released from the membrane, which leads to the cancer cells that quickly multiply. But even in such a case, side effects are triggered. “As long as you are mainly restricted to the cancer cells, is probably the more tragic; nevertheless, one should keep in mind,“ explains Walter to do this. (as)