Regulated cell death by crystals - new mechanism of action in gout disease discovered

Regulated cell death by crystals - new mechanism of action in gout disease discovered

Mechanism of direct "crystal-mediated cell death" identified
The deposition of crystals in the tissue is related to the development of various diseases, such as gout or atherosclerosis. An international team of researchers led by Professor Hans-Joachim Anders from the Ludwig Maximilians University in Munich (LMU) has now deciphered how the crystals trigger the death of cells. The researchers published their results in the journal "Nature Communications".

Crystals are the trigger for various common diseases. "Like the uric acid crystals in gout, they lead to a defense reaction of the immune system and trigger inflammation, at the same time they cause tissue cells to die," the LMU announcement. The research team led by Professor Anders from the medical clinic and polyclinic of the LMU has now succeeded in deciphering the mechanism that causes “crystal-mediated cell death”. According to the LMU, the current study results are "important for many diseases, including gout as well as atherosclerosis and some forms of acute kidney failure."

Crystals as the cause of tissue damage
Crystals have long been known as a possible cause of tissue damage, but the underlying mechanisms have remained unclear. "It is believed that the various diseases they trigger have a connecting pathomechanism," reports the LMU. So far, research has mainly focused on how crystals trigger inflammation. Because here the connecting factor between the different forms of crystal deposits was seen. The research team led by Professor Anders, on the other hand, has addressed the question of how the crystals can lead directly to cell death. For the first time, the scientists have succeeded in proving "that the crystals initiate a form of regulated necrosis in tissue cells," the LMU announced.

Active regulated mechanism leads to cell death
So far, cell death has been assessed as "rather than passive cell destruction" according to Professor Anders. However, based on their current study results, the researchers come to the conclusion that an actively regulated mechanism leads to direct cell death. They were able to decipher how the microparticles trigger cell death. The scientists have "investigated the molecular mechanism on kidney and connective tissue cells, among other things," reports the LMU. Using several crystals as an example, they were able to show that the microparticles always activate the same signaling pathway that leads to cell death. In addition, their data indicate that necrosis is the trigger for the inflammatory process and not inflammation that is the cause of the necrosis.

New treatment approaches possible
According to the researchers, current knowledge could also lead to the development of new treatment strategies. So far, medical treatment for diseases caused by crystals has relied on anti-inflammatory drugs. "The mechanism identified by Hans-Joachim Anders and his colleagues now offers a new goal for pharmacological research," said the LMU. According to Professor Anders, the signaling pathway discovered could be a new starting point for medication. “If it were prevented, this would prevent cell death directly triggered by crystals,” Anders continues. According to the latest study results, this should also prevent the development of chronic inflammation. Further research is now to show whether practical improvements for the treatment of patients can result from this, reports the Ludwig Maximilians University. (fp)

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