Anti-inflammatory drugs against Alzheimer's?

Alzheimer's therapy by anti-inflammatory?

20.12.2012

Researchers are discovering a new approach to Alzheimer's therapy with anti-inflammatory drugs. The research team led by Professor dr. 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, „which is involved in the development of chronic inflammation leading to dysfunction and death of nerve cells in the brain“ Alzheimer's patients, according to the press release of the University of Bonn. Their results have the scientists in the trade magazine „Nature“ released.

Alzheimer's disease is the most common form of dementia and is characterized by the gradual death of nerve cells in the brain, resulting in significant loss of memory and memory. According to Prof. Heneka, head of the Clinical Neurosciences working group at the Department of Neurology of the University of Bonn, and researcher at the German Center for Neurodegenerative Diseases (DZNE), it is already happening „Years before the first symptoms appear, in the brains of those affected to so-called plaques, which consist of incorrectly folded beta-amyloid peptides.“ In addition, in the brain cells of Alzheimer's patients are increasingly faulty tau protein deposits.zu find. As a result, certain brain cells are stimulated to produce more messenger substances, the one „signaling cascade“ trigger which ones „to a chronic inflammatory reaction and progressive loss of nerve cells“ explains Prof. Latz from the Institute for Innate Immunity of the University Hospital Bonn, who 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 nerve cells in the brain
In the course of their investigations, the scientists have demonstrated a substantially increased concentration of the caspase-1 enzyme in the brains of Alzheimer's patients as well as in genetically modified Alzheimer's mice. Caspase-1 plays „a key role“ in the activation of the inflammatory reaction, which ultimately leads to the death of the nerve cells, the scientists report.

The elevated levels are associated with chronic inflammatory reactions of immune cells in the brain. Both in humans and in the genetically modified mice, which served as a model of Alzheimer's disease, this finding has been confirmed. In addition to caspase-1, according to the researchers, the gene NLRP3 is crucially involved in the inflammatory signaling pathways that lead to the death of brain cells. When both the NLRP3 gene and caspase-1 were turned off in Alzheimer's mice, the animals had no inflammation in their brains and no memory loss, the researchers write. Also, elimination of the NLRP3 gene and caspase-1 would have deposited much less beta-amyloid peptides in the brain cells of the mice. „When the genes for caspase-1 and NLRP3 are muted, nerve cells and memory are apparently protected from typical Alzheimer's processes“, so the press release of the University of Bonn.

From previous studies it was already known that the Alzheimer's plaques are surrounded by so-called microglial cells. However, so far remained unclear, „what role inflammatory processes play in the development of the disease“, explained Douglas Golenbock of 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. By contact with the beta-amyloid plaques, a certain protein complex (the inflammasome) is activated, which in turn causes the increased release of caspase-1, according to the scientists in the cells. This enzyme in turn affects the release of the pro-inflammatory messenger interleukin-1-beta (IL-1b), which ultimately causes the inflammatory response in the brain of Alzheimer's patients.

Decisive insight into the development process of Alzheimer's
According to Prof. Heneka, the researchers are „to a crucial point in the development process of Alzheimer's encountered“ and in light of these findings, it seems promising to block the activity of the inflammasome. The results show a new starting point, „possibly in the development of new therapies for the treatment of Alzheimer's disease at an early stage“ can contribute, reports the University of Bonn. However, the scientists are „even at the stage of basic research, therapeutic success is therefore not yet foreseeable at the present time“, emphasized Prof. Heneka and added: „It is still a long way to go before initial clinical trials.“ However, potentially suitable drugs are already available or are being tested in clinical trials, said US researcher Douglas Golenbock. Their effect, however, must be increased significantly so that the inflammatory reaction in the brain of Alzheimer's patients could 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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Image: Martin Gapa