Alzheimer’s disease linked to overheating of brain cells

(ORDO NEWS) — Using temperature-sensitive fluorescent sensors, scientists measured the temperature inside the cells and found that the “sticking together” of beta-amyloid molecules (one of the causes of Alzheimer’s disease) causes a strong heating of neurons.

Neurodegenerative diseases remain one of the most acute medical problems of our time. They mainly affect the elderly and cause progressive neuronal death, with symptoms that may not be noticeable at first until cognitive, memory, motor function or other problems occur years later.

According to forecasts, the number of patients with neurodegenerations will increase several times in the coming decades.

Among them, the most common and actively studied was Alzheimer ‘s disease , the main symptom of which is progressive memory loss. Already, about 44 million people in the world have this diagnosis.

The two most important factors in the development of Alzheimer’s disease are tau and beta-amyloid. The former normally strengthens microtubules (“cell armature”), but in disease forms toxic inclusions inside neurons.

At the same time, beta-amyloid is a peptide formed when another protein is cleaved by special secretase enzymes. It can form toxic inclusions in the space between cells.

It is the second molecule, which is often called the “trigger” of the development of Alzheimer’s disease, that the staff of the University of Cambridge drew attention to in their new article in the Journal of the American Chemical Society .

It is known that some cells can release a large amount of heat – this is the so-called intracellular thermogenesis. It is not so easy to study it: hardly even the smallest thermometer can be introduced into a cell, especially so as not to damage it.

Therefore, scientists have created colored sensor molecules whose characteristic fluorescence time varies with temperature.

These are “polymer fluorescent thermometers” – substances that can be introduced into the cell without much harm to it. Now they are being used for the first time to investigate the pathogenesis of Alzheimer’s disease.

The authors of the work carried out experiments on cultures of human cells and noticed that the acquisition by beta-amyloid of an irregular conformation (mobile three-dimensional structure) and the “sticking together” of its molecules into filamentous fibrils is accompanied by strong heating.

High temperature, in turn, leads to the appearance of new toxic aggregates of beta-amyloid. As scientists suggest, this vicious circle contributes to a complex and yet poorly understood picture of the development of the disease.

Alzheimers disease linked to overheating of brain cells 2
The formation of beta-amyloid fibrils causes cell heating, which was studied using fluorescent probes

This discovery evokes culinary, but not the most pleasant associations among researchers. “Overheated cells are like scrambled eggs – as the temperature rises, the proteins in them begin to aggregate and can no longer perform their functions,” said Gabriel Kaminski Schierle, head of the team of scientists.

In addition, they were able to successfully stop beta-amyloid-induced heating with a new pharmacological agent (MJ040X).

It is possible that it could become the basis for an innovative treatment for Alzheimer’s disease – this is especially valuable because, despite decades of active research, its effective therapy has not yet been created .

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