Is restoring neuronal energy production the key to stopping neurodegeneration in Alzheimer’s disease?

In my mobile phone I stored a small collection of precious memories. A photograph of that beautiful cup of coffee that I drank in a tiny cafe in the city center, in the foam of which the friendly waiter drew a flower. A video from this summer in Asturias of me, laughing, trying to pour cider using a sort of siphon without losing anything (without much success, but with great pleasure). The audio message my friend sent me said very excitedly that her father’s surgery had gone well. Details of everyday life that you can return to in sad moments, so that the sweetness of memories dilutes the bitterness of the present.

Until the day when I had to perform a full emergency reset and all those files were lost. I was, of course, terribly upset, but it was the only option available if I wanted to continue using the phone. And, like a good stingy person, instead of scratching my pocket, I resort to whatever is necessary. Both the photos and videos are good, but The important thing about memories is that they will live with me forever.

But what if things weren’t like that? What if that cup of coffee, that summer in Asturias, or my friend’s voice are gradually erased? People with Alzheimer’s disease face this harsh reality. This disease affects the brain and causes progressive memory loss leading to absolute dependenceas any daily activity becomes an impossible task.

Science has been studying this disorder for many years in search of a way to stop it. We are gradually understanding all the intricacies of this cruel disease., something key to being able to cure it in the future. Recent research has contributed by focusing on the ability of neurons to obtain energy to try to stop neurodegeneration.

No fuel

The structure that is responsible for producing the energy necessary for the proper functioning of the cell is called mitochondria. A series of reactions called the Krebs cycle take place in mitochondria, involving various enzymes whose job is to produce molecules called ATP from glucose.

ATP is the main fuel of the cell, necessary for carrying out numerous chemical reactions on which the functioning of cells depends. Defects in mitochondria lead to very serious diseases such as Leigh syndrome or Alpers syndrome.

In patients with Alzheimer’s disease, among other abnormalities, it was observed that Neurons lose their ability to produce energy. The synapse, which is the connection between two neurons to transmit information, is vital to the proper functioning of the brain. Synapses require a lot of energy, so when ATP production is impaired, neurons cannot connect properly. This is one of the reasons why neurodegeneration occurs in the brain. memory is gradually erased.

Recent research has revealed the reason why neurons do not produce sufficient levels of energy. Apparently some enzymes involved in the Krebs cycle will be defective., which prevents them from performing their function. This prevents the formation of the succinate molecule needed to produce ATP.

Import fuel

Restoring the function of these defective enzymes is not easy, so a possible solution may be inject succinate into the cell as if it were a drug. This strategy is also challenging because the molecule has trouble penetrating cell membranes. But there is an analogue of succinate called dimethylsuccinate, which is able to penetrate cells. So the researchers injected it into neurons obtained from Alzheimer’s patients.

It was observed that this additional supply of succinate was able to give neurons the energy they were missing, restoring up to three-quarters of damaged synapses and thereby reducing neurodegeneration. Although this work is still at a very early stage, it suggests that Stopping brain decline by targeting neuronal energy metabolism may benefit Alzheimer’s patients. Let’s hope we can see these advances in the clinic soon, and the only memories that will be erased will be those on our phones, but never again in our minds.

-Go to the “Third Millennium” add-on.

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