Tokyo, October 25
Japanese researchers have discovered a new mechanism by which clumps of tau protein—found in brain cells—are created in the brain, killing brain cells and causing Alzheimer's disease.
A specific mutation to an enzyme called MARK4 changed the properties of tau, usually an important part of the skeletal structure of cells, making it more likely to aggregate, and more insoluble.
According to the study, published in the Journal of Biological Chemistry, getting to grips with mechanisms like this may lead to breakthrough treatments.
"Alzheimer's disease is said to be caused by the build-up of tangled clumps of a protein called "tau" in brain cells," said study authors from Tokyo Metropolitan University in Japan.
"These sticky aggregates cause neurons to die, leading to impairment in memory and motor functions. It is not yet clear how and why tau builds up in the brain cells of Alzheimer's patients," they added.
The research team has been exploring the role played by the MARK4 (Microtubule Affinity Regulating Kinase 4) enzyme in Alzheimer's disease.
When everything is working normally, the tau protein is an important part of the structure of cells or the cytoskeleton.
"To keep the arms of the cytoskeleton or microtubules constantly building and disassembling, MARK4 actually helps tau detach from the arms of this structure," the authors wrote.
Problems start when a mutation occurs in the gene that provides the blueprint for making MARK4.
Previous work had already associated this with an increased risk of Alzheimer's, but it was not known why this was the case.
The team artificially introduced mutations into transgenic Drosophila fruit flies that also produce human tau, and studied how the proteins changed in vivo.
They discovered that this mutant form of MARK4 makes changes to the tau protein, creating a pathological form of tau.
Not only did this "bad" tau have an excess of certain chemical groups that caused it to misfold, they also found that it aggregated much more easily and were no longer soluble in detergents.
This made it easier for tau to form the tangled clumps that cause neurons to degenerate.
MARK4 has also been found to cause a wide range of other diseases which involve the aggregation and buildup of other proteins.
That's why the team's insights into tau protein build-up may lead to new treatments and preventative measures for an even wider variety of neurodegenerative conditions, the study noted. IANS
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