Protein that wakes up the brain from sleep

According to a research published recently in The Journal of Experimental Medicine, a protein called ‘orexin’ could play a major role in the development of Alzheimer’s disease. Orexin is produced by the hypothalamus that causes wakefulness, while its absence causes narcolepsy, which is the ability to fall asleep spontaneously.

The researchers belong to Washington University, School of Medicine in St. Louis, and have been working with sleep disturbances and abnormalities, that possibly lead to the Alzheimer’s disease in old age. Alzheimer’s disease is a neurodegenerative disorder that causes progressive dementia and memory loss with the potential to hinder patients’ intellectual capabilities and ultimately lead to inability to perform everyday tasks.

“We should be looking hard at orexin as a potential target for preventing Alzheimer’s disease. Blocking orexin to increase sleep in patients with sleep abnormalities, or perhaps even to improve sleep efficiency in healthy people, may be a way to reduce the risk of Alzheimer’s. This is important to explore further,” said senior author David M. Holtzman who is the head of the Department of Neurology.

For this research, the investigators studied the brain function of mice and found that mice with sleep problems and sleep deprivation showed increased incidence of plaques. These plaques, composed of amyloid beta, are a characteristic finding in Alzheimer’s disease. And when they targeted a particular protein in the brain of mice, the progression of plaque formation slowed down significantly, resulting in decreased progression of disease. The off springs of the mice which lacked orexin had only half the number of plaques as their parents.

However, when the researchers artificially increased the levels of orexin in the brain, the mice developed wakefulness and more plaques. The researchers also noted one very important finding that inhibiting orexin in only part of the brain did not help diminish the progression of Alzheimer’s disease.

“The fact that orexin can only affect plaques when it also affects sleep means we will have to think carefully about how to target it for Alzheimer’s prevention,” Holtzman said. “But the declines in plaque levels that we saw in the mice were very strong, so we’re still very interested in exploring its potential for reducing risk.”


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