Daegu Gyeongbuk Institute of Science and Technology (DGIST, President Kook Yang), led by Professor Seong-Woon Yoo of the Department of Brain Science, investigated the phenomenon of excessive activation of microglia, the brain immune cells, in Alzheimer’s dementia, and suppressed the immune response to restore memory by suppressing the immune response. It was announced on the 14th that the drug had been discovered.
Alzheimer’s dementia is a degenerative brain disease that causes damage to nerve cells and loss of memory due to the accumulation of toxic proteins. There are no effective treatment or prevention techniques yet.
It is known that Alzheimer’s disease is expressed due to an increase in neuroinflammation due to the malfunction of microglia, which are responsible for innate immunity in our brain and spinal cord, but the exact mechanism has not been elucidated.
The research team produced mice expressing the gene mutation that causes Alzheimer’s disease, and observed that they sensitively respond to a very small amount of inflammatory stimuli or amyloid beta that are harmless to normal mice. It was confirmed that memory loss occurs due to such an excessive immune response.
As a result of the study, it was confirmed that the cause of the excessive immune response is that the promoter region of the circadian gene ‘REV-ERBα’, which suppresses the expression of cytokines, is DNA methylated and the expression of REV-ERBα is reduced. We found that demethylation of the promoter suppressed microglia hyperactivation while restoring REV-ERBα expression.
In addition, by reinventing the drug, ‘Chlorpromazine’ revealed the effect of restoring memory ability by restoring REV-ERBα expression and suppressing hyperimmune reactions, suggesting a new treatment direction for Alzheimer’s dementia. The new drug candidate discovered this time has completed domestic and international patent applications and is currently preparing for technology transfer to OATC.
Professor Yoo Seong-woon said, “By elucidating a new mechanism between Alzheimer’s dementia and the microglia immune response, we have laid the foundation for further in-depth dementia treatment research.”
This research result, which was supported by the Brain Science Training Technology Development Project of the Ministry of Science and ICT and the OATC, was published in the world-renowned academic journal Nature Communications on the 13th. The first author of this study is Nam Hye-ri, a Ph.D. student.
Daegu = Reporter Jeong Jae-hoon jhoon@etnews.com
