When it comes to losing functional memory, slowing down the rate of loss is not enough, as remembering recent experiences and forming new memories sets us apart from most other forms of life. With this in mind, the researchers tested a small, light-activated molecule in mice and successfully removed clumps of amyloid protein that are present in the brains of Alzheimer’s patients. This was the result of a new study published in the journal Brain.
While this is still a long way from being launched for human applications, the technique could offer an alternative approach to immunotherapy – in addition to other uses to treat other diseases associated with similar amyloids.
Light activated catalyst destabilizes proteins associated with Alzheimer’s symptoms
The research involved injecting the molecule directly into the brains of living mice suffering from Alzheimer’s disease, followed by using special probes to shine light directly into the brains of the mice for 30 minutes a day, every day, for a week. According to chemical analysis, the brain tissue of the mouse showed a significantly reduced amyloid protein from the treatment. In addition, further experiments with human brain samples donated by Alzheimer’s patients appeared to support the potential for possible use in humans.
“The importance of our study is to develop this technique to target the amyloid protein to improve clearance by the immune system,” said Yukiko Hori, a University of Tokyo who also co-authored the newly published research with Embargoed report Interesting engineering shared. The tiny molecule that was developed in this research is known as a photooxygenation catalyst and appears to act in a two-part process against Alzheimer’s disease.
It starts when the catalyst destabilizes the amyloid plaques through oxygenation (or the addition of oxygen atoms) – which causes a molecule to lose its stability by affecting the chemical bonds that hold its structure together. We also see this process in laundry detergents known as “oxygen bleach”. In contrast to detergents, this catalyst was specially developed for the folded structure of amyloid and probably works by cross-linking certain parts of the molecule – so-called histidine residues. The catalyst remains inert until activated externally via near infrared light. This means that future research could include new ways of delivering the catalyst into the body by injecting it into the bloodstream to reach target areas.
Future Alzheimer’s treatment might just involve a shot and light
Once the catalyst is activated, immune cells in the brain called microglia remove the destabilized amyloid in a traditional process that removes damaged cells and debris that surround healthy cells. While observing mouse cells grown in a dish, the researchers observed how the microglia ate up oxygenated amyloid and break it down into acidic integral compartments of the cells.
“Our catalyst binds to the amyloid-specific structure, not a unique genetic or amino acid sequence, so this catalyst can be applied to other amyloid deposits as well,” said Taisuke Tomita, professor who led the new study at the University of Tokyo. This is important because 4,000 people are diagnosed with diseases associated with amyloid outside of the human brain – collectively called amyloidosis, according to the American Society of Clinical Oncology.
Combining light with a catalyst in a process known as photooxygenation can likely destroy amyloid protein – whether or not it was formed in the body. And while some types of Alzheimer’s treatments successfully slow the formation of new amyloid plaques, the ability to eliminate plaques that are already covering the human brain is vital because amyloid builds up for years before the onset of symptoms – which is easy means slowing the rate growth can only delay the inevitable.
The University of Tokyo team is currently trying to modify the groundbreaking catalyst design so that it can be activated by shining a light through a human skull. This could work because it is near infrared light and not visible wavelengths of our modern day life. We are far from mass adoption of this technology, but this could point to a future where it will be as easy to prevent people with Alzheimer’s disease from losing their memory function well into old age as using a near-infrared light activated catalyst inject. pointed straight to the head.