A mammalian cage stained with fluorescent polymer thermometers and falsely stained based on temperature gradients. Credit: Chyi Wei Chung

Researchers have shown that the aggregation of amyloid beta, one of the two key proteins involved in Alzheimer’s disease, causes cells to overheat and “fry like eggs.”

Researchers at the University of Cambridge used sensors that are small and sensitive enough to detect temperature changes inside individual cellsand found that how amyloid beta improperly folds and sticks together, it causes cells overheat.

In an experiment using human cell lines, researchers found heat that emits beta-amyloid aggregation can potentially cause aggregation of other, healthy beta-amyloids, causing the formation of more aggregates.

In the same series of experiments, the researchers also showed that beta-amyloid aggregation can be stopped and lower cell temperature by adding a drug compound. Experiments also show that the compound has potential as a therapeutic agent for Alzheimer’s disease, although extensive testing and clinical trials will be required first.

Researchers say their analysis can be used as diagnostic tool for Alzheimer’s disease or for screening potential drug candidates. The results are reported in Journal of the American Chemical Society.

Alzheimer’s disease affects approximately 44 million people worldwide, and there are currently no effective methods of diagnosis or treatment. In Alzheimer’s disease, beta-amyloid and another protein called tau accumulate in tangles and plaques, known together as aggregates, causing brain cells die, and the brain shrinks. This leads to memory losspersonality changes and difficulty performing daily functions.

It is a difficult disease to study as it has been evolving for decades, and a definitive diagnosis can only be made after examining brain tissue samples after death. It is still unknown what biochemical changes inside the cell lead to beta-amyloid aggregation.

In the research group of Professor Gabriele Kaminski Shirle at the Department of Chemical Engineering and Biotechnology in Cambridge, they investigated the possible relationship between temperature and beta-amyloid aggregation in human cells.

The field of study of changes in temperature inside a cell is known as intracellular thermogenesis. This is a new and challenging field: scientists have developed sensors that can measure changes in temperature, but no one has ever tried to use these sensors to study conditions such as Alzheimer’s disease.

“Thermogenesis has been linked to cellular stress“That may contribute to further aggregation,” said Chi Wei Chung, the study’s first author. “We believe that when there is an imbalance in cells, for example, when the concentration of beta-amyloid is too high and it starts to accumulate, the cell temperature rises.”

“Overheating a cell is like frying eggs – when it heats up, the proteins start to stick together and become dysfunctional,” said Kaminski Shirle, who led the study.

The researchers used tiny temperature sensors, called fluorescent polymer thermometers (FTP), to study the relationship between aggregation and temperature. They added amyloid beta to human cell lines to start the aggregation process, and used a chemical called FCCP as a control because it is known to cause fever.

They found that when beta-amyloid began to form filamentous aggregates called fibrils, the average temperature of the cells began to rise. The increase in cell temperature was significant compared to cells in which no beta-amyloid was added.

“As the fibrils begin to lengthen, they release energy in the form of heat,” said Kaminski Shirle. “Aggregation of beta-amyloid requires quite a lot of energy to get started, but once the aggregation process begins, it accelerates and releases more heat, allowing more aggregates to form.”

“Once the aggregates are formed, they can leave the cell and be captured by neighboring cells, infecting healthy beta-amyloid in those cells,” Chung said. “No one has previously shown this link between temperature and aggregation in living cells.”

Using a drug that inhibits beta-amyloid aggregation, the researchers were able to pinpoint fibrils as the cause of thermogenesis. It was previously unknown whether this phenomenon was due to protein aggregation or potential damage to mitochondria – “batteries” that feed cells.

The researchers also found that the rise in cell temperature could be mitigated by treating them with aggregation inhibitors, emphasizing its potential as a therapeutic agent for Alzheimer’s disease. disease.

Laboratory experiments have been supplemented by computational simulations that describe what can happen to beta-amyloid in the intracellular environment and why it can lead to an increase in intracellular temperature. The researchers hope their work will motivate new research that includes a variety of physiological parameters.

Alzheimer’s disease can start inside nerve cells

Additional information:
Chyi Wei Chung et al., Intracellular aggregation of Aβ42 leads to cellular thermogenesis, Journal of the American Chemical Society (2022). DOI: 10.1021 / jacs.2c03599

Citation: Alzheimer’s disease causes cell overheating and “frying like eggs” (2022, May 31, 2022), obtained May 31, 2022 from https://phys.org/news/2022-05-alzheimer-disease-cells -overheat-eggs.html

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