Researchers at Cambridge used small sensitive sensors to identify temperature variations inside particular cells. They found that because of clumps and, amyloid-beta misfolds, cells overheat. Researchers used cell lines to test the hypothesis that heat from amyloid-beta combination could cause amyloid beta to assemble, leading to more damage.
In addition, the researchers demonstrated that the drug compound could be added to stop amyloid-beta combination and lower cell temperatures. Although the experiments recommend that the combination may be a potential therapeutic for Alzheimer‘s, further clinical trials and tests are needed. Researchers believe their assay can be used to diagnose Alzheimer’s disease or screen for possible drug candidates.
These results are published in the American Chemical Society journal. There are no current treatments or diagnostics for Alzheimer’s disease, which affects approximately 44 MN people around the world. Alzheimer’s disease is caused by build-up of tau protein amyloid-beta into plaques and tangles, also recognized as aggregates. Because of this brain cells die and brain shrinks. Death of brain cells causes personality changes, memory loss, and difficulty performing daily tasks.
Because it can develop over many decades, it isn’t easy to study. A complete diagnosis can possible after a study of dead brain cells. It’s unknown how biochemical changes in cells can lead to amyloid-beta to combine. The research group of Prof. Gabriele Kaminski Schierle at Cambridge’s Department of Biotechnology and Chemical Engineering has been studying the link between amyloid-beta aggregation and temperature within human cells.
Intracellular thermogenesis is the study of temperature variations in a cell. A new challenging field. Scientists have created sensors that measure temperature changes, but nobody has tried them to study Alzheimer’s disease. Chyi Wei-Chung, the study’s original author, stated that thermogenesis is associated with cellular stress. This may encourage further aggregation. “We believe that cellular temperatures rise when cells are in an abnormal state, such as when amyloid-beta concentrations are slightly too high.
Kaminski Schierle, the researcher, said that overheating cells is similar to frying eggs – when it heats up, the proteins begins to clumping together and become inoperable. The researchers discovered that amyloid-beta began to form fibrils-like aggregates, thread-like. This caused the cells to experience an increase in temperature. The cells with amyloid-beta were more sensitive to the rise in temperature than those without it.
Kaminski Schierle stated that fibrils start to elongate and release heat as energy. However, once it starts, it accelerates and emits more heat. This allows for more aggregates. Chung stated that once aggregates are formed, it can be released from cells and taken up by neighbouring cells. This could infect healthy amyloid-beta in cells. “This link between temperature and aggregate formation in live cells has never been demonstrated before,” Chung said.
Researchers can identify the causes of thermogenesis by using a drug that inhibits amyloid-beta aggregation. This phenomenon was previously unknown. Alzheimer’s disease is known for the combination of Aβ42. It is unidentified what biochemical changes happen in cells that will eventually lead to Aβ42 aggregate. Thermogenesis is linked to cellular stress, which can promote aggregation.
Intracellular thermometry is performed using fluorescent polymeric thermometers. It shows that Aβ42 clumping occurs in live cells and causes a rise in average cell temperatures. The temperature increase is reduced by treatment. This is free of mitochondrial harm, which can otherwise cause thermogenesis. This diagnostic assay could be used to screen small-molecule inhibitors for amyloid proteins in physiologically appropriate settings. We use classical molecular dynamics to model Ab peptides to interpret our observations and encourage the development of future models.
This is explained by the presence of ions, the morphology and hydrogen-bonding interactions of the amyloid proteins with water, as well as the surrounding environment.
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