The mechanism of early dementia development has been identified

Using an animal model, American scientists from the Gladstone Institutes demonstrated the existence of a relationship between progranulin protein deficiency and the development of frontotemporal dementia (frontotemporal type dementia), an early-onset form of dementia similar to Alzheimer's disease.

Frontotemporal dementia is a deadly disease that causes the destruction of neurons in the frontal and temporal lobes of the brain. Its fundamental difference from Alzheimer's disease is that in the latter, the damage zones are localized mainly in memory centers in the hippocampus. Early symptoms of frontotemporal dementia include personality changes such as erratic or compulsive behavior. Subsequently, patients have problems with speech and reading, and often develop long-term memory loss. As a rule, the disease is diagnosed at the age of 40-65 years, and death occurs within 2-10 years after diagnosis. To date, there are no drugs that can slow down, suspend or reverse the progression of frontotemporal dementia.

A new hope for patients with this disease appeared in the form of results obtained by researchers working under the guidance of Professor Robert V. Farese. They demonstrated how the progranulin protein prevents hyperactivation of microglial cells. With a low level of this protein, microglial cells get out of control, and their hyperactivity causes a chronic inflammatory reaction, over time leading to the destruction of neurons and the appearance of adverse symptoms.

In a normal state, microglial cells localized in the central nervous system secrete progranulin. Earlier studies have shown that with traumatic injuries to the organs of the central nervous system, progranulin, as well as microglial cells, accumulates in the area of damage. This led the authors to the idea that both components play certain roles in the body's response to injury to nervous tissue. To find out the relationship between them, scientists have planned a series of experiments.

First, they created genetically modified mice with no progranulin in their bodies, and observed the reactions of the animals' brains to the effects of toxins, comparing these reactions with the reactions of the brains of control group mice. As expected, the toxins destroyed brain cells in mice of both groups, but animals without progranulin lost twice as many cells.

After that, in experiments on cultures, the authors blocked the secretion of progranulin by microglia and observed the interaction of such glial cells with neurons. It turned out that in the presence of modified migroglia, significantly more neurons died than in the presence of intact glial cells.

Subsequent experiments made it possible to uncover the mechanisms underlying the identified mechanism. Microglia is the first line of defense of the central nervous system. When its cells register the presence of toxins or damage, they trigger a protective inflammatory reaction, which, in the case of uncontrolled flow, can damage neurons. As it turned out, the controlling function in this case is performed by progranulin, in the absence of which chronic inflammation leads to the death of neurons.

In cultural experiments, the researchers managed to suppress inflammation and prevent the death of neurons by increasing the concentration of progranulin. The next stage of the work will be testing this approach on animal models. The authors hope that in the future the results of their work will form the basis of a therapeutic strategy for suppressing the progression of frontotemporal dementia, and possibly new approaches to the treatment of severe neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.

Article by Lauren Herl Martens et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury published in the Journal of Clinical Investigation.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Gladstone Institutes:
Gladstone Scientists Identify Biological Mechanism that Plays Key Role in Early-Onset Dementia.

15.10.2012