Power of light and oxygen clears Alzheimer's disease protein in live mice

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A small, light-activated molecule recently tested in mice represents a new approach to clearing clumps of amyloid protein found in the brains of Alzheimer’s patients. If perfected in humans, the technique could be used as an alternative approach to immunotherapy and the treatment of other diseases caused by similar amyloids.

The researchers injected the molecule directly into the brains of living mice with Alzheimer’s disease and then used a special probe to shine light into their brains for 30 minutes a day for a week. Chemical analysis of mouse brain tissue showed that the treatment significantly reduced amyloid protein. Results from additional experiments with human brain samples donated by Alzheimer’s patients supported the possibility of future use in humans.

“The importance of our study is to develop this technique to target amyloid protein activation and improve clearance by the immune system,” said Yukiko Hori, professor at Tokyo University and co-first author of the research recently published in Brain.

The small molecule that the research team developed is known as a photooxygenation catalyst. It appears to treat Alzheimer’s disease in two steps.

First, the catalyst destabilizes the amyloid plaques. Oxygenation or the addition of oxygen atoms can make a molecule unstable by changing the chemical bonds that hold it together. Laundry detergents or other cleaning products known as oxygen bleach use a similar chemical principle.

The catalyst targets the folded structure of amyloid and likely cross-links certain parts called histidine residues. The catalyst is inert until activated with near infrared light. Therefore, in the future, researchers envision that the catalyst could be released throughout the body by injection into the bloodstream and aimed at specific areas with light.

Second, the destabilized amyloid is then removed by microglia, immune cells in the brain that remove damaged cells and debris outside of healthy cells. Using mouse cells growing in a dish, the researchers observed how microglia engulf oxygenated amyloid and then break it down in acidic compartments within the cells.

“Our catalyst binds to the amyloid-specific structure, not to a unique genetic or amino acid sequence, so this catalyst can also be applied to other amyloid deposits,” said Professor Taisuke Tomita, who led the project at the University of Tokyo.

The American Society of Clinical Oncology estimates that 4,000 people in the United States are diagnosed each year with diseases caused by amyloid outside the brain, collectively known as amyloidosis. (www.cancer.net/cancer-types/amyloidosis/statistics)

The photooxygenation catalyst should be able to remove amyloid protein no matter when or where it was formed in the body. Although some existing treatments for Alzheimer’s disease can slow the formation of new amyloid plaques, clearing existing plaques is especially important in Alzheimer’s disease because amyloid begins to aggregate years before symptoms appear.

The research team is now working on modifying the design of the catalytic converter so that it can be activated by exposure to light through the skull.

This research is an peer-reviewed experimental study using mice and human tissue samples. The human temporal cortex brain samples used in this study were from the Alzheimer’s Disease Core Center (ADCC) and the Center for Neurodegenerative Disease Research (CNDR) at the University of Pennsylvania in the United States

Nanoparticles help disentangle amyloid beta plaques from Alzheimer’s disease

More information:
Photooxygenation using a biocompatible catalyst reduces amyloid β levels in the Alzheimer’s model Brain (2021). DOI: 10.1093 / brain / awab058

Journal information:
Brain provided by the University of Tokyo

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