A joint research team has disclosed mechanisms concerning neuronal cell death and cell and molecular level, which constitute the cause of dementia.

The researchers reported Tuesday that severe reactive astrocytes, or star-shaped cells, cause neuronal deaths, which induced Alzheimer’s disease in the early stage. 

The image shows the mechanism of neuronal cell death caused by severe reactive astrocytes, leading to Alzheimer’s disease. (IBS)
The image shows the mechanism of neuronal cell death caused by severe reactive astrocytes, leading to Alzheimer’s disease. (IBS)

The research team, led by Lee Chang-joon, a director at the Institute for Basic Science (IBS), Ryu Hoon, a researcher at Brain Science Institute at the Korea Institute of Science and Technology (KIST), revealed the mechanism by observing the astrocytes appearing in the early stages of dementia. 

Alzheimer's disease worsens over a long period. The disease progression cannot be stopped once the neuronal cells start dying in the late stage, implying the significance of understanding the cause and process before the death begins. In an animal model developed by the joint research team, researchers confirmed that severe reactive astrocytes irreversibly killed neurons and advanced Alzheimer's disease.

The research team found that excessive hydrogen peroxide originated from monoamine oxidase B (MAO-B) in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, and cognitive impairment.

For many years, drug developers have been developing therapies for Alzheimer's disease based on the belief that the toxic amyloid-beta protein can cause the disorder. However, they could not explain why patients continue to experience Alzheimer's disease, with or without the existence of amyloid-beta.

The research team will operate a new strategy targeting MAO-B or hydrogen peroxide to treat Alzheimer's to solve the enigma.

"Controlling abnormal activities of reactive astrocytes in Alzheimer patients' brains are important because those cells cause neuronal damage," Ryu said.

Lee also said, "We are glad to find that reactive astrocytes, which were considered only a by-product of Alzheimer's, are the main cause of neuronal cell death, hoping the study results to help patients suffering the disease."

The study, titled "Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer's disease via H2O2-production," was published in Nature Neuroscience on Nov. 17.

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