Scientists at the University of California School of Medicine in San Diego have discovered a steroid hormone that suppresses inflammation of brain tissue. The discovery, published in the journal Cell, is of great importance for understanding the pronounced inflammatory reactions characteristic of many neurodegenerative diseases.

The discovery that the steroid hormone adiol (ADIOL, 5-androsten-3?-17?-diol), the precursor of androgens and estrogens, modulates the microglia-inducible inflammation, can ultimately lead to new methods of treating patients with neurodegenerative diseases in which inflammation plays Role of pathological factor. In addition, ADIOL levels in the blood and other body fluids may be useful for predicting the risk or reactions to medications that mimic its effect.

Although neurons are the main cells of the nervous system, their normal functioning is possible only with the support of other types of cells, including microglial cells and astrocytes. Microglia cells help the central nervous system respond to infections and injuries. Under normal conditions, they are at rest, imperceptibly, but constantly monitoring the surrounding microenvironment to signal signs of microbial contamination and tissue damage. If such signs are found, microglia initiates an inflammatory reaction, giving impetus to the work of the immune system and tissue repair processes. Astrocytes enhance the immune response induced by microglia cells.

Activation of microglia and astrocytes is vital for an effective immune response and repair of damage, but if the inflammation caused by these cells is uncontrolled or continues for too long, it can lead to damage and death of neurons. Out of control inflammation is characteristic of many neurodegenerative diseases such as Parkinson's disease, HIV-associated dementia, Alzheimer's disease and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease, Charcot's disease), as well as for certain inflammatory diseases, for example, for disseminated Sclerosis.

The results of the last study show that in a healthy brain, the inflammation of the microglia is modulated by the production of the steroid hormone ADIOL, which causes the support cells to return to a state of rest. ADIOL functions by interacting with a transcription factor called the estrogen receptor beta, which derives its name due to its similarity to the estrogen alpha receptor and the ability to bind to the female sex hormone with estrogen. Unexpectedly, while binding to ADIOL causes the estrogen beta receptor to perform anti-inflammatory instructions for microglia and astrocytes, binding to estrogen does not cause such consequences. Therefore, the action of estrogens can actually be considered antagonistic to the anti-inflammatory effect of ADIOL.

Professor of the Department of Cellular and Molecular Medicine and the Department of Medicine, Doctor of Medicine and Philosophy Christopher Glass (Christopher Glass) and his colleagues made their discovery on the basis of initial research conducted jointly with Dr. John Katzenellenbogen of the University of Illinois, Urbana-Champaign. The Katzenellenbogen Laboratory has developed a number of synthetic small molecules that bind very strongly and specifically to the estrogen receptor beta.

Scientists tested each of these compounds and found several potent inhibitors of inflammatory reactions of microglial and astrocytes. When one of these compounds was tested in vivo, it turned out that it significantly suppressed brain inflammation and caused persistent remission on a mouse model of multiple sclerosis.

Although estrogen itself can have a neuroprotective effect, the lack of ability to induce the anti-inflammatory activity of the estrogen beta receptor has led to the search for endogenous molecules that could have an activity similar to synthetic compounds. Eventually, as an endogenous regulator of the estrogen receptor beta, scientists identified ADIOL. It is remarkable that the amount of ADIOL, which can synthesize microglia, is regulated by signals controlling the strength and duration of inflammatory reactions.

"We consider it possible that mutations in the genes encoding the key enzymes of ADIOL production, or the inappropriate regulation of these genes, can contribute to pathological forms of inflammation," says Professor Glass.

These findings suggest that women are more prone to some inflammatory diseases, such as multiple sclerosis, since higher levels of estrogen potentially act as antagonists to the anti-inflammatory effects of ADIOL in the brain. Similar reasoning can probably help explain some of the side effects of estrogens on the brain with their appointment to the postmenopausal period.

However, as Professor Glass observes, there are still many studies to be carried out. The exact relationship between inflammation and neurodegenerative diseases, for example, has not yet been established. Scientists have identified ADIOL-estrugnuyu connection only on the mouse model of multiple sclerosis. In the next studies, Glass and his colleagues plan to analyze this relationship in animal models of Alzheimer's and Parkinson's and HIV-dementia.

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