Researchers have identified new gelatinase substrates that play a role in the function of the astroglial barrier. In neuroinflammation, immune cells like leukocytes traverse the blood-brain barrier, with a crucial factor being the gelatinases matrix metalloproteinase (MMP)-2 and -9. The specific su
In the microscope image, astrocytes are stained green and immune cells are stained red. The basement membranes of the vessels are seen in white. Credit: University of Münster / University Hospital Bonn
In neuroinflammation, immune cells like leukocytes traverse the blood-brain barrier, with a crucial factor being the gelatinases matrix metalloproteinase -2 and -9. The specific substrates these enzymes act upon during this process have been unidentified until recently. Utilizing a sensitive mass spectrometry-based secretome method, scientists from theand Bonn University Hospital have now successfully identified hundreds of molecules that are cleaved from the cell surface of astrocytes.
However, studies in multiple sclerosis show that disease symptoms do not develop until immune cells have also penetrated the astroglial layer. “Evidence suggests that MMP-2 and MMP-9 have both positive and negative effects on the BBB. Therefore, deciphering their substrate specificity at the brain parenchymal boundary will contribute to the understanding of molecular processes essential for astroglial barrier function,” said Prof. Sorokin.Identifying the enzyme cleavage sites is a challenge.
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