Every cell in the body is surrounded by a membrane similar to a fat film, the so-called plasma membrane.
This also contains numerous proteins that span the membrane from outside to inside and act as sensors for the cell.
When these proteins encounter certain molecules on the outside, they generate a signal on the inside of the membrane and thus regulate certain reactions within the cell.
Other membrane proteins are able to transport certain substances into the cell.
Researchers at the University of Bonn have investigated the influence of gamma secretase on cellular fat metabolism and found that this could be a possible starting point for future cancer therapies.
However, hopes for new approaches to Alzheimer’s were rather disappointed.
The results of the study were published in the English language journal “Life Science Alliance”.
The so-called gamma-secretase has been investigated for a long time as a starting point for the treatment of Alzheimer’s and cancer.
A new study now shows how gamma secretase influences fat metabolism in cells and provides important insights into this special mechanism.
Important function of gamma secretase
Gamma secretase regulates the fat metabolism in the brain
Gamma-secretase assumes important functions in the release of membrane-anchored signal proteins.
For example, gamma-secretase breaks up discarded membrane proteins into individual parts, which are then disposed of.
It is precisely this function that secretase has been particularly interesting for researching Alzheimer’s for two decades.
Many brain cells contain a protein called APP in their membrane.
When the gamma secretase APP breaks up into smaller parts, one of the fragments is released into the brain fluid.
This is the so-called Abeta peptide.
This is the main component of the plaques that occur in the destroyed brain areas of Alzheimer’s patients.
“It was originally hoped that inhibition of gamma secretase would be able to slow Alzheimer’s disease,” explains Prof.
Dr.
Jochen Walter from the University of Bonn in a press release.
However, this has not yet worked.
What is the task of the plasma membrane?
If the gamma secretase fails, the membrane gradually becomes clogged.
As a result, certain molecules can no longer be introduced into the cell as well, which leads to serious consequences, in which APP also plays a key role, the researchers report.
If gamma secretase is inhibited in cell cultures, APP accumulates in the membranes, which hinders the uptake of lipoproteins from the environment.
This mechanism triggers a fatal process.
So-called lipoproteins are particles of proteins and fat-like molecules, the lipids.
If too little lipid gets into the cells, the cells assume that there is a lipid deficiency, the rectification of which increases the cell’s own lipid synthesis.
However, the inhibitors of gamma secretase are more promising for the treatment of cancer, according to the researchers.
There are proteins in the cell membrane that stimulate our cell division.
If gamma secretase is switched off in tumor cells, they are no longer released from the membrane, which means that the cancer cells can no longer multiply as quickly.
But even in such a case, side effects are triggered.
“As long as they are mainly limited to cancer cells, that’s probably not a big problem; nevertheless, you should keep an eye on them, ”explains Walter.
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“Other studies have already shown that a disturbance in lipid metabolism in the brain can also contribute to the development of Alzheimer’s disease,” explains Professor Walter.
The current study provides information about the mechanism by which this can be done.
Inhibiting gamma-secretase may therefore have exactly the opposite effect that one hopes for from this measure, the expert adds.
When secretase is inhibited, a central regulator of lipid synthesis called LXR is strongly activated.
Lipids are then partially transported out of the cell, but due to the impaired lipoprotein uptake, the cell does not receive any feedback about the successful measure.
As a result, lipids continue to be produced, leading to the accumulation of fat droplets.
This contributes to fatty formation inside the cell, which can also disrupt important cell functions.
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