Gene Identified That May Unlock the Secret of Vulnerability to Adult Brain Diseases Such as Dementia

A team of Korean researchers has identified a brain immune gene that determines individual susceptibility to adult-onset brain diseases such as dementia. This discovery is expected to provide important clues for uncovering the causes of various brain immune responses, including degenerative brain diseases, and for developing therapeutic strategies.

On September 24, KAIST announced that a research team led by Professor Inkyung Jung from the Department of Biological Sciences, together with a team led by Professor Wonseok Jung, Associate Director of the Vascular Research Center at the Institute for Basic Science (IBS) and also a professor at KAIST, has, for the first time in the world, identified that a specific gene plays a key role in regulating adult brain immune responses during the development of astrocytes.

(From left) Professor Wonseok Jung, PhD candidate Hyunji Park, Dr. Sungwan Park, Professor Inkyung Jung. Provided by KAIST

The joint research team applied three-dimensional epigenome analysis technology (a technique for analyzing the activation and deactivation of DNA genetic information) to comprehensively analyze the transcriptome, chromatin accessibility, and three-dimensional genome interactions (a technology to observe how DNA folds and interacts in space) during astrocyte development. Through this, they identified 55 key gene regulatory proteins (transcription factors) involved in the maturation of astrocytes.

In particular, when they precisely analyzed the gene regulatory programs of astrocytes-cells with a high proportion in the brain and spinal cord of mouse models-at different developmental stages, they found that the NR3C1 (Glucocorticoid Receptor) gene acts as a crucial regulator of long-term immune response suppression during the postnatal developmental stage.

The researchers explained that NR3C1 serves as the "most important switch" when a baby's brain first develops. However, the presence or absence of NR3C1 did not have a significant effect on the development of the brain during infancy or childhood. In contrast, in adulthood, the absence of NR3C1 led to excessive inflammatory responses in the brain in cases of autoimmune diseases (conditions where the immune system attacks the brain), thereby exacerbating the disease.

Based on these findings, the joint research team concluded that NR3C1 functions as an "epigenetic priming" controller-similar to an engine preheating button-preparing the immune switch in the infant brain in advance. Thanks to this mechanism, the brain is protected from excessive immune responses in adulthood.

Epigenetic priming control refers to the process by which the NR3C1 gene, even if not immediately expressed, sets the switch in advance so it can be activated instantly when needed.

Wonseok Jung, Associate Director at IBS, stated, "Our joint research team has, for the first time, established that the immune function of astrocytes is regulated by epigenetic memory." He added, "These findings will help elucidate the causes of degenerative brain diseases such as Alzheimer's disease in the future."

Inkyung Jung, Professor of Biological Sciences at KAIST, commented, "This study is significant because it confirms that the specific developmental window (temporal regulatory window) of astrocytes can determine vulnerability to adult and elderly brain diseases." She added, "Research based on three-dimensional genome structure is expected to contribute to understanding new mechanisms underlying immune-related brain diseases such as multiple sclerosis and to the development of therapeutic strategies."

This research was conducted with Dr. Seongwan Park and PhD candidate Hyunji Park from the Department of Biological Sciences at KAIST as co-first authors. The results were recently published online in the international journal Nature Communications.

This content was produced with the assistance of AI translation services.