June 12, 2019
Keio University School of Medicine
A research group led by Senior Lecturer Koji Sugata and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, has discovered a mechanism necessary for the formation of the brain's barrier function, which prevents the invasion of foreign substances.
Approximately 15% of the blood flowing through the body is present in the brain, where it transports nutrients and removes waste products. Therefore, to maintain the delicate functions of nerve cells and the brain, mechanisms are needed to prevent harmful substances from leaking out of blood vessels into the brain and to quickly push unwanted substances back into the bloodstream. This barrier function, possessed by the capillaries in the brain, is called the blood-brain barrier, and it is known that its function declines due to brain inflammation, brain tumors, and even aging. However, many of the mechanisms that form and maintain the blood-brain barrier have remained unclear.
In this study, we worked to elucidate this mechanism using the brain of the fruit fly (Drosophila) and its barrier function as an experimental model, as it has long been widely used as a model organism in the fields of medical and biological sciences. It is known that humans and Drosophila share many similarities in the mechanisms that strictly limit contact between the brain and blood (hemolymph in flies) and in the genes that control them.
As a result of this research, we discovered that a proteolytic enzyme belonging to the matrix metalloproteinase (Mmp) group is essential for the proper formation of the blood-brain barrier's mechanism. Previously, this enzyme was known as a "destroyer" that degrades the function of the blood-brain barrier by breaking down collagen and other substances around blood vessels during brain inflammation and other conditions.
This study clarifies the molecular mechanisms in the formation of the blood-brain barrier and is expected to contribute to the future treatment of brain diseases, neural regenerative medicine, and the improvement of the blood-brain barrier's function when inducing vascular endothelial cells from iPS cells and other sources.
The results of this research were published in the online edition of "iScience" on Tuesday, June 11, 2019 (U.S. Eastern Time).
Please see below for the full press release.