‘We have found an alternative to estrogen receptors in the brain,’ said Christopher Glass, University of California at San Diego.Although MS is a very complex disease, the results suggest that drugs targeting receptors ER might actually terminate the inflammation that is associated with the disease, Saijo said. The same principle might work in treating other neurodegenerative diseases associated with inflammation, including Parkinson’s disease, Alzheimer’s and HIV-associated.
‘Although the estrogen receptor (ER) have been implicated in the etiology of multiple sclerosis, no clear molecular mechanism to link them to relapsing-remitting MS,’ wrote David Gosselin and Serge Rivest in a comment. ‘Now in this issue of Cell, Saijo and colleagues may have filled this gap.’
In addition to explaining why women develop MS more often than men, Gosselin and Rivest continues, the results also suggest that drugs and environmental factors, such as estrogen analogues of plant origin may also encourage the development of disease.
The findings may also help explain the strong sexual orientation in multiple sclerosis, which disproportionately affects relatively young women. ‘When you see ER estradiol receptor, they can start ADIOL leaving the brain more susceptible to inflammation,’ Saijo said. In other words, ADIOL estradiol and compete for ER and estradiol competition typically wins.
ADIOL levels in the cerebrospinal fluid or blood may also be a useful biomarker of inflammation, they said. The results also suggest that genetic variants in this direction, including the enzyme needed to produce ADIOL, should be considered as prime candidates for MS susceptibility genes.
‘The possibility arises from our study that estradiol may antagonize the effects of anti-inflammatory ADIOL,’ Glass said. ‘This can lead to a change in the balance of inflammatory to anti-inflammatory.’
Estrogen receptors are primarily known to activate gene expression programs, he said. In this case, however, estrogen receptors are essential to turn off genes that would otherwise lead to chronic inflammation.
Both ER and ER respond to the hormone estradiol, the main form of estrogen in humans. Glass and study first author Kaoru Saijo now that ER also responds to a second hormone called ADIOL well. It is converted by special enzymes ADIOL from its precursor DHEA in microglia.
Researchers have discovered an unexpected role for estrogen receptors in the brain, keeping under control the inflammation. The results presented May 13 issue of Cell Press journal Cell may have important implications for the treatment of (MS) and many other neurodegenerative diseases. They may also help explain why women are three times more likely to develop MS than men, researchers say.