Can Alzheimer's be treated with anti-inflammatory drugs?
Researchers discover a new approach to Alzheimer's therapy with anti-inflammatories. Eicke Latz and Professor Dr. Michael T. Heneka from the University of Bonn and Douglas Golenbock from the University of Massachusetts (USA) have succeeded in identifying a new signaling pathway “that is involved in the development of chronic inflammation, which leads to the malfunction and death of nerve cells in the brain “Alzheimer's patient leads, says the press release from the University of Bonn. The scientists have published their results in the specialist journal "Nature".
Alzheimer's disease is the most common form of dementia and is characterized by the gradual death of nerve cells in the brain, which leads to considerable losses in memory formation and memory. According to Prof. Heneka, head of the Clinical Neurosciences working group at the Neurological Clinic of the University of Bonn and researcher at the German Center for Neurodegenerative Diseases (DZNE), there are so-called plaques in the affected person's brain years before the first symptoms appear, which consist of misfolded beta-amyloid peptides. ”In addition, faulty tau protein deposits are increasingly to be found in the brain cells of Alzheimer's patients. This stimulates certain brain cells to produce more messenger substances that trigger a “signal cascade”, which “leads to a chronic inflammatory reaction and progressive loss of nerve cells,” explained Prof. Latz from the Institute for Innate Immunity of the University Hospital Bonn also works as a researcher at the DZNE and the University of Massachusetts Medical School (USA). This loss of nerve cells accelerates the development of Alzheimer's dementia.
Inflammatory reactions lead to the death of the nerve cells in the brain. In the course of their investigations, the scientists detected a substantially increased concentration of the enzyme Caspase-1 both in the brain of Alzheimer's patients and in genetically modified Alzheimer's mice. The scientists report that Caspase-1 plays a "key role" in activating the inflammatory response, which ultimately leads to the death of the nerve cells.
The increased values are associated with chronic inflammatory reactions of the immune cells in the brain. This finding was confirmed both in humans and in the genetically modified mice that served as a model of Alzheimer's disease. In addition to caspase-1, the researchers say that the NLRP3 gene is crucially involved in the inflammatory signaling pathways that cause brain cells to die. If both the NLRP3 gene and the caspase-1 were switched off in the Alzheimer mice, there were no inflammations in the brains and no memory impairments in the animals, the scientists write. If the NLRP3 gene and caspase-1 were switched off, much less beta-amyloid peptides would have been deposited in the brain cells of the mice. "If the genes for Caspase-1 and NLRP3 are muted, the nerve cells and memory are apparently protected from the typical Alzheimer's processes," said the press release from the University of Bonn.
It was already known from previous studies that the Alzheimer's plaques are surrounded by so-called microglial cells. However, it has so far remained unclear “what role inflammatory processes play in the development of the disease,” explained Douglas Golenbock from the University of Massachusetts. The microglial cells as immune cells of the central nervous system have the task of eliminating potentially pathogenic factors such as viruses, bacteria, but also damaged cells and deposits in the brain. According to the scientists, contact with the beta-amyloid plaques activates a certain protein complex (the inflammasome) in the cells, which in turn causes the increased release of caspase-1. This enzyme in turn influences the release of the inflammatory neurotransmitter interleukin-1-beta (IL-1b), which ultimately causes the inflammatory response in the brain of Alzheimer's patients.
Decisive insight into the developmental process of Alzheimer's disease According to Prof. Heneka, the researchers have "found a crucial point in the developmental process of Alzheimer's disease" and in view of these findings it seems promising to block the activity of the inflammasome. The results show a new starting point "that could possibly contribute to the development of new forms of therapy for the treatment of Alzheimer's disease at an early stage", reports the University of Bonn. However, the scientists are "still at the stage of basic research, so therapy success is not yet foreseeable at the present time", emphasized Prof. Heneka and added: "It is still a long way to go before the first clinical studies." However, there are potentially suitable ones Drugs are already available or are currently being tested in clinical trials, explained US researcher Douglas Golenbock. However, their effect must be significantly increased so that the inflammatory response in the brain of Alzheimer's patients can be suppressed. However, there is hope in the future to treat the previously incurable Alzheimer's disease with the help of anti-inflammatories. (fp)
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