Suppressing the immune response will help with Alzheimer's disease?
Researchers from the German Center for Neurodegenerative Diseases and the University of Bonn, together with colleagues from Spain and the United States, identified a protein that is a potential target for the treatment of Alzheimer's disease. The molecular complex they study is a component of the immune system and the driving force of inflammatory reactions developing in brain tissue. Blocking its activity may be a promising direction for the development of new therapeutic approaches.
A complex of molecules called NLRP3-inflamasome (NLRP3 inflammasome, from inflame –ignite, catch fire) consists of several proteins and acts as a kind of alarm. Its activation leads to the start of a chain reaction, the result of which is the mobilization of immune cells and the release of compounds that trigger the mechanisms of inflammation. This process can be triggered by infections, which are subsequently suppressed by the immune system.
Diagram of the signaling pathway of the formation of an inflammasome,
initializing the inflammatory process in bacterial infection
(from the Mutagenetix database)
However, in the case of Alzheimer's disease, activation of this signaling pathway can have negative consequences: damage and death of nerve cells. The end result of this is a deterioration in the functioning of the brain and the extinction of human mental abilities.
Alzheimer's disease is accompanied by the appearance of so-called amyloid plaques in brain cells, which are aggregates of pathologically altered beta-amyloid protein molecules. The ability of these plaques to activate NLRP3-inflamasomes has been demonstrated previously in experiments on individual cells. However, the consequences of increased activation of this complex for the brain have so far been unclear.
The results of postmortem examination of the brain tissue of patients with Alzheimer's disease and mouse models of this disease provided exhaustive evidence that NLRP3-inflamasome plays a decisive role in the development of Alzheimer's disease. In both cases, the researchers found an activated form of this complex.
In another experiment, scientists removed the genes that trigger the production of NLRP3-inflamasomes from a mouse model of Alzheimer's disease. As a result, the animals developed only relatively mild symptoms of the disease. Moreover, the content of amyloid plaques in their brain tissue was less than in the brain tissue of the control group mice.
The authors believe that the discovery of this mechanism opens up new possibilities for combating Alzheimer's disease by blocking the activity of NLRP3-inflamasoma. They have already started searching for compounds that can have the desired effect, and hope to start testing them in the laboratory next year.
Article by Michael T. Heneka et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice published in the journal Nature.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the German Center for Neurodegenerative Diseases:
Alzheimer’s Disease: Cutting off Immune Response Promises New Approach to Therapy.
26.12.2012