As people grow older, the blood-brain barrier becomes more fragile. This tightly packed network of blood vessels normally shields the brain from harmful substances circulating in the bloodstream. Over time, however, it can become leaky, allowing damaging compounds to enter brain tissue. The result is inflammation, which is linked to cognitive decline and is commonly seen in disorders such as Alzheimer's disease.
Several years ago, the research team discovered that exercising mice produced higher levels of an enzyme called GPLD1 in their livers. GPLD1 appeared to rejuvenate the brain, but there was a mystery. The enzyme itself cannot cross into the brain, leaving scientists unsure how it delivered its cognitive benefits.
The new research provides an answer.
How GPLD1 Reduces Brain Inflammation
The scientists found that GPLD1 influences another protein known as TNAP. As mice age, TNAP builds up in the cells that form the blood-brain barrier. This buildup weakens the barrier and increases leakiness. When mice exercise, their livers release GPLD1 into the bloodstream. The enzyme travels to the blood vessels surrounding the brain and removes TNAP from the surface of those cells, helping restore the barrier's integrity.
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