Alzheimer's, so exercise prevents it thanks to a protein that protects memory

In addition to its action on metabolism and weight loss. In addition to the prevention of diabetes and cardiovascular disease, it also has a positive impact on quality of life and mood. Regular physical activity, without demanding too much of the body through over-exertion, is also a lifesaver for the central nervous system, helping to prevent neurodegeneration. Now research has uncovered a new piece in the jigsaw puzzle of knowledge associating the lower risk of Alzheimer's disease with maintaining good physical activity (in addition to social activity, of course). In practice, there would exist a kind of pathway between the body and the brain that, thanks to the action of regular movement, helps to rejuvenate memory. How? By sealing the blood-brain barrier, even in old age (as happens in youth), and thus preventing toxic compounds and inflammation-promoting products from entering the nervous system. This is all thanks to the combined action of an enzyme, GPLD1, and the TNAP protein, with the former somehow keeping the brain's 'customs' young thanks to physical activity.

The study, which also opens up interesting perspectives on pharmacological mechanisms potentially active on this mechanism, was conducted on mice by researchers at the University of California at San Francisco and published in Cell. Basically, the scientists, led by Saul Villeda, associate director of the Bakar Aging Research Institute at the same university, discovered a possible biological pathway that intervenes in the positive relationship between exercise, thinking and memory, passing through a sort of 'rejuvenation' of the brain's protective mechanisms. Everything would be associated with the action of the blood-brain barrier, a real 'border' that tends to widen with advancing senescence and thus to lose its function as a curtain that cannot be crossed by harmful substances circulating in the blood. Over time, the excessive permeability of this protective structure encourages the passage of toxic substances that promote inflammation, which has been observed in various neurodegenerative conditions such as Alzheimer's disease.

We are still in the animal, it must be said. But research, building on observations from some time ago, shows how we can try to rejuvenate the blood-brain barrier and thus protect the brain. Everything goes through an enzyme called GPLD: animals that do more physical activity produce more of it in the liver. Beware, however: GPLD1, although it may have a brain-rejuvenating effect, cannot reach the brain. So what? So with this study, it was discovered that the protection of GLPD1 fostered by regular exercise goes through an action on another protein, called TNAP. As the animal ages, TNAP accumulates in the cells that form the blood-brain barrier. This accumulation weakens the barrier and increases permeability. When mice exercise regularly, their liver releases GPLD1 into the blood. The enzyme comes to 'clean' removes TNAP from the surface of the barrier cells, helping to restore their integrity. And thus make it 'younger'.

GPLD1 is a kind of invisible scissor. And it cuts specific proteins from the cell surface. Therefore, once it was discovered that blood-brain barrier cells can harbour various possible targets for GPLD1, the researchers saw that only TNAP was eliminated. Caution though. This is a very important protein: young mice genetically modified to produce an excess of TNAP in the blood-brain barrier showed memory and cognitive problems similar to those observed in older animals. By reducing TNAP levels in the mice by 2 years, equivalent to 70 human years, the blood-brain barrier became less permeable, inflammation decreased and the animals performed better in memory tests. 'This finding shows how relevant the organism is to understanding the decline of the brain with age,' Villeda commented in a note from the American university. The results suggest that the development of drugs that can reduce proteins such as TNAP could offer a new strategy to restore the blood-brain barrier, even after it has been weakened by ageing.