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

Mechanism of direct "crystal-mediated cell death" identified
The deposition of crystals in the tissue is associated with the development of various diseases such as gout or atherosclerosis. An international team of researchers led by Professor Hans-Joachim Anders of the Ludwig-Maximilians-Universität München (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 cause of various widespread diseases. "They lead, such as the uric acid crystals in gout, to a defense reaction of the immune system and trigger inflammation, at the same time they cause the death of tissue cells," said the LMU. The research team led by Professor Anders of the Medical Clinic and Polyclinic of the LMU has now succeeded for the first time in deciphering the mechanism that causes "crystal-mediated cell death". The current study results are according to the LMU "for many diseases of importance, including in addition to gout atherosclerosis and some forms of acute renal failure."

Crystals are associated with various diseases such as gout. Scientists have now deciphered a mechanism that causes crystals to undergo regulated necrosis. (Image: DamienGeso / fotolia.com)

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

Active regulated mechanism leads to cell death
So far, the dying of the cells according to Professor Anders was rated "rather than passive cell destruction". However, on the basis of 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 the death of cells. The scientists have "investigated the molecular mechanism of 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 activate the same pathway that leads to cell death. In addition, their data indicate that necrosis is the trigger for the inflammatory process and not the inflammation cause of necrosis.

New treatment approaches possible
According to the researchers, the current findings could also lead to the development of new treatment strategies. So far, in the medical treatment of diseases that are triggered by crystals, set on anti-inflammatory. "The mechanism identified by Hans-Joachim Anders and his colleagues now offers a new target for pharmacological research," says the LMU. According to Professor Anders, the discovered signaling pathway could be a new starting point for drugs. "If he is stopped, that would prevent the directly triggered by crystals cell death," Anders continues. According to the latest study results, it should also be possible to prevent the development of a chronic inflammation. Further research will now show whether this can result in practical improvements for the treatment of patients, reports the Ludwig-Maximilians-Universität. (Fp)