An erroneous target?
Amyloid plaques in Alzheimer's disease – "cleaning" biological debris?
One of the main signs of Alzheimer's disease is the accumulation of amyloid plaques from pathological protein in the brain tissues, which is considered the main cause of the disease. However, methods aimed at getting rid of them repeatedly fail in clinical trials. A recent study not only explains the possible cause of the failures of antiamyloid therapy, but also radically changes the views on the formation of dense clusters of pathological protein.
Article by Huang et al. Microglia use TAM receptors to detect and engulf amyloid β plaques is published in the journal Nature Immunology.
In Alzheimer's disease, a neurodegenerative disease that develops mainly in old age, a person loses memory, his thinking worsens, and behavior changes. The result is the development of senile dementia. And against the background of increasing life expectancy due to the achievements of medicine, this disease, like other age-related diseases, is becoming more common: according to forecasts, by 2050 the number of such patients in the world will reach 100 million.
Why is Alzheimer's disease still incurable? A quarter of a century ago, an amyloid hypothesis of the development of this disease was proposed, associated with the deposition of beta-amyloid protein in brain tissues. Amyloid plaques can be of different types, the most common are diffuse, representing poorly organized amorphous "clouds", as well as dense, with a compact center.
The latter serve as objects of special attention of scientists: several attempts were made to create a cure for Alzheimer's disease based on monoclonal antibodies capable of reducing the number of dense amyloid plaques, but the results of clinical trials were at least ambiguous.
It is believed that both types of amyloid plaques are formed spontaneously in the brain, and their microglia cells – immune brain cells - destroy them. Microglia should work like other macrophages: these cells have receptor proteins of the TAM family, with which they recognize and then "eat" their obsolete cell. At the same time, the cell to be destroyed must signal this with a certain molecule on the surface – a "death signal".
It is this molecular signal that is inherent in amyloid formations. Recently, scientists from the Salk Institute for Biological Research (USA), using laboratory mice serving as a model of Alzheimer's disease, found out that microglial cells carrying receptors THERE are able to absorb diffuse beta-amyloid. Inside these cells, the absorbed protein fibrils condense, and it is from them that a dense plaque is formed.
According to the researchers, we are talking about a protective mechanism by which the structural "organization" of diffuse beta-amyloid, which is more dangerous for neurons, occurs, as a result of which the intercellular space is cleared of this "garbage". Moreover, they suggest that an increase in the activity of receptors THERE in microglial cells and the associated acceleration of the formation of dense plaques helps to alleviate the symptoms of Alzheimer's disease. Scientists plan to test this hypothesis experimentally.
In conclusion, the authors suggest to stop looking for ways to destroy amyloid plaques, and to engage in methods that will reduce the synthesis of pathological protein or improve its excretion from brain tissues.
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