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The power of light and oxygen removes Alzheimer’s disease proteins in living mice

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A small photoactivating molecule recently tested in mice represents a new approach to eliminating amyloid protein clumps found in the brains of patients with Alzheimer’s disease. When completed in humans, this technique can be used as an alternative approach to immunotherapy and in the treatment of other diseases caused by similar amyloids.

Researchers injected the molecule directly into the brain of a living mouse with Alzheimer’s disease and then used a special probe to illuminate the brain for 30 minutes each day for a week. Chemical analysis of mouse brain tissue showed that treatment significantly reduced amyloid protein. The results of additional experiments using human brain samples provided by patients with Alzheimer’s disease confirmed their potential for future use in humans.

“The importance of our research is to develop this technology that targets amyloid proteins to increase the clearance of amyloid proteins by the immune system,” said the co-lead author of a recently published study at the University of Tokyo. Yukiko Hori said. brain..

The small molecule developed by the research team is known as a photooxygenation catalyst. It seems to treat Alzheimer’s disease in a two-step process.

First, the catalyst destabilizes the amyloid plaque. Oxygenation, or the addition of oxygen atoms, can destabilize a molecule by altering the chemical bonds that bind it. Other cleaners known as laundry detergents or oxygen bleaches use similar chemical principles.

The catalyst is designed to target the folded structure of amyloid and may function by cross-linking specific moieties called histidine residues. Since the catalyst is inactive until it is activated by near-infrared light, in the future it will be delivered systemically by injecting the catalyst into the bloodstream and light will be used to target specific areas. Researchers believe that it can be done.

Second, destabilized amyloid is removed by microglia, the immune cells of the brain that remove the outer debris of damaged and healthy cells. Using mouse cells growing in a dish, researchers observed that microglia swallowed oxygenated amyloid and degraded in the intracellular acidic compartment.

Professor Taisuke Tomita, who led the project at the University of Tokyo, said, “Our catalyst binds to amyloid-specific structures rather than unique gene or amino acid sequences, so apply this same catalyst to other amyloid deposits. You can do it. “

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

Photooxygenation catalysts need to be able to remove amyloid proteins regardless of when and where they are formed in the body. Elimination of existing plaques is especially important in Alzheimer’s disease, as some existing treatments for Alzheimer’s disease can delay the formation of new amyloid plaques, but amyloid begins to aggregate years before symptoms appear. is.

The research team is currently working on changing the design of the catalyst so that it can be activated by shining light through the skull.

This study is a peer-reviewed experimental study using mouse and human tissue samples. The human temporal lobe brain samples used in this study were from the Alzheimer’s Disease Core Center (ADCC) and Neurodegenerative Disease Research Center (CNDR) at the University of Pennsylvania, USA.


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For more information:
Biocompatible catalytic photooxygenation reduces amyloid β levels in Alzheimer’s disease models. brain (2021). DOI: 10.1093 / brain / awab058

Journal information:
brain

Provided by the University of Tokyo

Quote: The power of light and oxygen was obtained from https://medicalxpress.com/news/2021-04-power-oxygen-alzheimer-disease-protein.html on April 13, 2021 in live mice (2021). , April 13) Clear Alzheimer’s disease protein

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