(CN) — Along with developing the first 3D cell culture models of Alzheimer's disease, a research team found that an exercise-induced hormone might be able to combat the disorder by helping those who may not be able to exercise.
The Massachusetts General Hospital-based research team created Alzheimer's models that display two of the condition’s major hallmarks — identified as tau tangles and the generation of amyloid beta deposits in the researchers’ study, published Friday in Neuron.
In their study, the team pointed out that other research on the subject found that physical exercise could reduce amyloid beta deposits in various mouse models of Alzheimer's, though the researchers were unsure of what mechanisms were in place. To that end, the researchers focused on irisin.
Irisin is a hormone that increases its circulating levels through exercise, regulates glucose and lipid metabolism in fat tissue and accelerates the browning of white fat tissue to increase energy expenditure, according to the study. Researchers also noted in the study that Alzheimer's patients, whether human or mouse, have reduced levels of irisin in their brains,
Se Hoon Choi and Eun Hee Kim of the Genetics and Aging Research Unit at Massachusetts General, along with their colleagues, applied the irisin hormone to their 3D cell culture models of Alzheimer's disease so the researchers could see if irisin possessed a causal role in linking exercise and the reduction of amyloid beta deposits.
“First, we found that irisin treatment led to a remarkable reduction of amyloid beta pathology,” said Choi in a statement. “Second, we showed this effect of irisin was attributable to increased neprilysin activity owing to increased levels of neprilysin secreted from cells in the brain called astrocytes.”
Neprilysin, an amyloid beta-degrading enzyme, was found to have elevated levels in the brains of mice with Alzheimer's when they exercised or otherwise underwent conditions that reduced amyloid beta. While uncovering details about the mechanisms of irisin’s connection to reduced amyloid beta levels, the researchers also found that irisin binds to integrin αV/β5 as a receptor on astrocytes, triggering the cells to increase the levels of neprilysin.
Furthermore, the researchers said that when irisin bound itself to this receptor, it led to the reduction of signaling the pathways that involved two key proteins known as extracellular signal-regulated kinase and signal activator of transcription 3. According to the study, the reduction of this signaling was critical for irisin to enhance neprilysin.
Additionally, other research found that injecting irisin into the bloodstream of a mouse could allow the hormone to reach the brain, which senior author and director of the Genetics and Aging Research Unit Rudolph Tanzi said could open two possibilities for how the study of irisin can help Alzheimer's patients.
“One is to develop irisin into a drug where we mimic the effects of exercise by injecting irisin into the body and getting it to go into the brain and the amyloid beta that causes Alzheimer's. More than that, it emphasizes the need for exercise. Aside from all of the exciting drug possibilities, it shows how exercise itself dramatically reduces your risk for Alzheimer’s disease,” said Tanzi said during a phone interview.
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