Korea Brain Research Institute Identifies Protein That Rejuvenates the Brain Without Exercise

Exercise is the healthiest way to activate brain cells and enhance cognitive function. However, those who have difficulty with physical activity due to aging or illness may find it hard to expect the benefits of exercise. Now, a protein that can rejuvenate the brain without exercise has been identified as a substitute.

The Korea Brain Research Institute announced on April 27 that a joint research team led by Dr. Park Hyungju of the Neurovascular Unit Group and Professor Kim Jongseo of the Department of Biological Sciences at Seoul National University has discovered 'Serpina1e', a key protein secreted by muscles during exercise and delivered to the brain, and for the first time in the world, has elucidated the mechanism by which it enhances cognitive function.

Korea Brain Research Institute

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The joint research team used genetically modified mouse models and advanced mass spectrometry (proteomics) technology to precisely analyze myokines secreted by muscles during exercise, confirming that the muscle-derived protein 'Serpina1e' significantly increased in the blood of mice that exercised for four weeks.

Furthermore, they found that injecting 'Serpina1e' into mice that did not exercise increased the number of neurons in the hippocampus and improved cognitive function, similar to the effects seen in mice that actually exercised.

Conversely, when this protein was inhibited, the cognitive improvement effects of exercise disappeared, proving that 'Serpina1e' is an essential substance that directly mediates the cognitive benefits of exercise.

Serpina1e, which penetrates the brain's protective barrier (the blood-brain barrier, BBB) and reaches the hippocampus, increases the expression of brain-derived neurotrophic factor (BDNF) and promotes nerve cell regeneration, leading to substantial improvements in cognitive abilities.

This provides decisive evidence for the previously shrouded 'direct communication between muscle and brain', suggesting that drug delivery systems capable of acting on the brain without separate carriers may be possible.

The greatest achievement of this study is the demonstration that Serpina1e can directly cross the blood-brain barrier (BBB), which has been the greatest hurdle in developing treatments for brain diseases.

Dr. Park stated, "This study is significant because it clearly presents the pathway by which a specific protein derived from muscle acts directly on the hippocampus by crossing the brain barrier through the bloodstream. The joint research team is currently verifying therapeutic effects in models of aging and neurodegenerative diseases, and we expect that this will lead to the development of new drugs to overcome cognitive decline."

Professor Kim said, "With advanced protein analysis technologies, we were able to identify key factors mediating the effects of exercise. I hope this research will serve as an impetus to advance studies on 'body-brain' interactions."

Meanwhile, this research was supported by the Mid-career Researcher Program of the Ministry of Science and ICT and the National Research Foundation of Korea, as well as institutional projects of the Korea Brain Research Institute and the Institute for Basic Science. The results were published in the international journal 'Nature Communications.'

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