An image of brain immune cells called microglia clustering around a build-up of toxic beta-amyloid . Credit: LKCMedicine/NTU Singapore
Microglia tend to be damaged in people with the disease, which makes them less capable of clearing cellular toxic waste. To restore the clean-up function, the scientists “switched off” their inefficient metabolism by preventing a key enzyme from attaching to energy-generating parts of the immune cells.
The researchers’ findings, which were published in Proceedings of the National Academy of Sciences in February 2023, are in line with one of the goals of the NTU 2025 strategic plan to respond to the needs and challenges of healthy living and aging.
The research team showed that without the translocator protein, microglia from mice with Alzheimer’s had an energy problem and could not remove the beta-amyloid, which resulted in the disease worsening in the mice. To manipulate the enzyme’s role in microglia energy production, the NTU researchers developed a light-activated tool. Their tool involves shining blue light onto a genetically modified version of the hexokinase-2 enzyme to “switch off” one of its functions.
Such drugs could target the hexokinase-2 enzyme, which is found in the brain’s microglia at high levels in people with Alzheimer’s disease.