Science & Technology, Singapore (Commonwealth Union) – Alzheimer’s disease is a progressive and degenerative brain disorder that affects memory, thinking, and behavior. A key hallmark of Alzheimer’s disease is the accumulation of amyloid plaques and tau protein tangles in the brain. These abnormal protein deposits lead to the loss of connections between nerve cells and eventually cause the death of brain cells.
A study conducted by the Nanyang Technological University (NTU) has demonstrated a new way to incite brain immune cells to clear toxic waste associated with Alzheimer’s disease (AD). Researchers discovered a ‘metabolic switch’ in the brain’s immune cells that can be a target for treating AD. A recently found “energy switch” in the immune cells of the brain could bring about the formation of drugs for AD. NTU scientists made the discovery following the blocking and turning off this “switch”, brain immune cells known as microglia had the ability to take away toxic proteins that can gather up and lead to AD.
Microglia are a type of immune cells found in the central nervous system (CNS), including the brain and spinal cord. They are the resident macrophages of the CNS and play a crucial role in the brain’s immune defense system. They constantly monitor their surroundings for signs of injury or infection, and they can quickly respond to any damage or changes in the brain’s environment.
In addition to their immune function, microglia also play an important role in the development and maintenance of the brain. They are involved in synaptic pruning, which is the process by which weak or unnecessary connections between neurons are eliminated, allowing for more efficient communication between neurons.
Microglia have a tendency of being damaged in persons with AD, making them less able to clear cellular toxic waste. The clean-up function restoring, where researchers “switched off” their inefficient metabolism by blocking a key enzyme from attaching to energy-generating components of the immune cells. The results from lab experiments can lead to the formation of drugs able to specifically target metabolism in brain immune cells for treating AD, making up 60 to 70% of all dementia cases across the world.
Despite the availability of ways to treat AD, definitive cures are unavailable for the condition, generally affecting the elderly and impairing an individual’s ability to think. The results of the study, appeared in Proceedings of the National Academy of Sciences this year, were on par with one of the goals of the NTU 2025 strategic plan to respond to the requirements and challenges of healthy living along with ageing.
Dr Yeo Tianrong, senior consultant neurologist at the National Neuroscience Institute in Singapore who was not a part of the study said that Assistant Professor Barron and her team had the ability gain new insights to piece together the puzzle of energy generation required for microglia to take away beta amyloid in the brain.
“Importantly, they found that the displacement of hexokinase-2 led to improved energy production and enhanced the microglia’s ability to get rid of beta amyloid. This is of significance as the strategy of hexokinase-2 displacement represents a potential therapeutic target for improved beta amyloid removal by the microglia,” explained Dr Yeo.
He further stated “The study by Asst Prof Barron’s team highlights the possibility that, one day, we can harness the intrinsic capability of microglia to mop up toxic beta amyloid by reconfiguring their energy generating framework.”
Further studies is set to have researchers conduct experiments to confirm there observations in cells with the possibility of physiological conditions having an unexpected effect on the outcome.
The approach of maintaining metabolism in microglia utilizing the light-activated tool will further be useful for research on how energy production functions in cells for other diseases and conditions, such as diabetes and obesity.