Scientists have identified a naturally occurring enzyme that can break down a key component of the brain plaques characteristic of Alzheimer's disease. The finding may provide researchers with new opportunities to understand what goes wrong in the brains of Alzheimer's patients and could one day help them seek new therapies.
Researchers at Washington University School of Medicine in St. Louis showed earlier this summer that the enzyme, matrix metalloproteinase 9 (MMP-9), degrades abnormally aggregated proteins known as amyloid fibrils, a main ingredient of brain plaques. In the brain, MMP-9 is made by support cells known as astrocytes.
MMP-9 is already well-known because of its links to cancer metastases, vascular disease, arthritis and other pathologies. Scientists called the new link to Alzheimer's encouraging, noting that previously identified enzymes only degrade a smaller, nonaggregated component of Alzheimer's plaques.
"We already knew of three enzymes that break down amyloid beta (Abeta), a protein fragment that clumps together with itself to form the fibrils," says Jin-Moo Lee, M.D., Ph.D., assistant professor of neurology. "But the thinking up until now had been that Abeta might be clumping together so tightly that the fibrils were indestructible."
In a new study, appearing October 25 in The Journal of Neuroscience, Lee's group found that disabling the mouse gene for MMP-9 increased levels of Abeta in the spaces between brain cells. The finding proves that MMP-9 contributes to clearance of Abeta from extracellular spaces and suggests its dysfunction could potentially contribute to the development of Alzheimer's.
"MMP-9 and other enzymes like it are secreted from brain support cells and active in the spaces outside of cells, and that's where we saw an increase in Abeta levels in the mice that lacked the gene for MMP-9," Lee notes. "That's relevant to Alzheimer's because all the amyloid plaques are extracellular, and the forma
Contact: Michael C. Purdy
Washington University School of Medicine