Thought It Was Poison, But It Helps Cleanse the Brain?... The 'Twist' of a Dementia Substance [Health LAB]

[Financial News] Domestic researchers have discovered a new principle for reactivating cleaning cells in the brain associated with dementia.
According to the Korea Institute of Science and Technology (KIST) on the 16th, a research team led by Principal Researcher Ryu Hoon of the KIST Brain Disease Research Group and Principal Researcher Hyunbeom Lee of the Biomolecular Recognition Research Center, in collaboration with Professor Junghee Lee's team at Boston University School of Medicine, identified a new pathway that cleans up proteins causing dementia by enhancing the waste removal ability of microglia, which are brain immune cells.
According to the research team, Alzheimer's dementia is a disease in which toxic proteins, such as amyloid beta, accumulate in the brain and damage nerve cells. Although research to remove these toxic proteins has been ongoing, it has not been easy to solve the fundamental problem that the brain's cleaning function itself declines with age.
The research team focused on 'quinolinic acid,' a metabolite in the brain. Although quinolinic acid is known to damage nerve cells at high concentrations, the team confirmed for the first time in the world that at low concentrations, it actually exhibits a 'reverse effect' that enhances the cleaning ability of microglia.
When a small amount of quinolinic acid stimulates microglia, key enzymes in the pathway that produces phospholipids, which constitute the cell membrane, are activated. The newly produced phospholipids (PE phospholipids) make the cell membrane flexible and bind to proteins involved in the autophagy process of waste removal, helping immune cells better capture and break down toxic proteins in the brain. This is a 'hormesis' effect, where small amounts of harmful substances or toxins actually enhance the body's defense capabilities. The research team named this new cleaning pathway 'GAP'.
When low concentrations of quinolinic acid were locally administered to the brains of an actual Alzheimer's dementia mouse model, amyloid beta plaques in the hippocampus were significantly reduced within a few days. Damaged neuronal connections were also restored, and short-term and long-term memory abilities improved to the level of normal mice.
This study could lead to a new dementia treatment strategy that selectively activates only the brain's 'cleaning system' operated by quinolinic acid, rather than using quinolinic acid itself as a therapeutic agent. It is evaluated that this approach has the potential to be applied not only to the development of new drugs that enhance the ability of microglia to remove waste products, but also to the treatment of other degenerative brain diseases where toxic proteins accumulate, such as Parkinson's disease and Huntington's disease.
This achievement presents a new paradigm for the treatment of degenerative brain diseases by focusing on the brain's self-recovery and cleansing capabilities, and is the fruit of mission-oriented research pursued by the KIST Brain Science Institute with the goal of "realizing national brain health by overcoming intractable brain diseases."
"We have revealed that a metabolite, previously known only as a substance that exacerbates dementia, can actually act as a signal that enhances the regenerative capacity of brain immune cells at low concentrations," said Ryu Hoon, a principal researcher at KIST. "This is significant in that it presents a new dementia treatment strategy utilizing the metabolic and cleaning functions of brain immune cells."
"KIST Principal Researcher Hyunbeom Lee stated, 'We plan to discover therapeutic candidate substances that selectively activate the microglia's cleaning system and pursue preclinical verification and technology transfer in cooperation with pharmaceutical and biotech companies.'"
The results of this study were published in the latest issue of the international academic journal 'Signal Transduction and Targeted Therapy' (IF 81.2, top 0.2% of JCR).
[email protected] Yeon Ji-an Reporter