Soft-boiled neurons
Alzheimer's disease has been linked to overheating of brain cells
Mikhail Orlov, Naked Science
Neurodegenerative diseases remain one of the most acute medical problems of our time. They affect mainly the elderly and cause progressive death of nerve cells, and at first the symptoms may be unnoticeable, and only years later there are cognitive disorders, memory, motor function or other problems.
According to forecasts, the number of cases of neurodegeneration in the coming decades will increase several times. Among them, the most common and actively studied was Alzheimer's disease, the main symptom of which is increasing 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 protein and beta-amyloid. The first one normally strengthens microtubules ("cellular reinforcement"), but in case of illness forms toxic inclusions inside neurons. At the same time, beta-amyloid is a peptide formed when another protein is broken down 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" for the development of Alzheimer's disease, that the Cambridge University researchers drew attention to in their new article in the Journal of American Chemical Society (Chung et al., Intracellular Aß42 Aggregation Leads to Cellular Thermogenesis).
It is known that some cells can emit a large amount of heat — this is the so-called intracellular thermogenesis. It is not so easy to investigate it: hardly even the smallest thermometer can be inserted into the cage, especially so as not to damage it. Therefore, scientists have created colored sensor molecules, the characteristic fluorescence time of which varies depending on temperature. These are "polymer fluorescent thermometers" — substances that can be introduced into the cell without much harm to it. Now they have been used for the first time to study the pathogenesis of Alzheimer's disease.
The authors of the work conducted experiments on human cell cultures and noticed that the acquisition by beta-amyloid of an irregular conformation (mobile three-dimensional structure) and the "sticking" 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. Scientists suggest that this vicious circle contributes to a complex and still poorly understood picture of the development of the disease.
This discovery causes culinary, but not the most pleasant associations among researchers. "Overheated cells resemble scrambled eggs — with increasing temperature, proteins in them begin to aggregate and can no longer perform their functions," she said Gabriel Kaminski Schierle, head of the team of scientists.
In addition, they were able to successfully stop the beta-amyloid-induced heating with a new pharmacological drug (MJ040X). It is possible that it can become the basis for an innovative way to treat 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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