Scientists from Tokyo Metropolitan University found a new mechanism by which clumps of tau protein 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.
Getting to grips with mechanisms like this may lead to breakthrough treatments.
The research is published in the Journal of Biological Chemistry and was conducted by Kanae Ando et al.
Alzheimer’s disease is a life-changing, debilitating condition, affecting tens of millions of people worldwide. It is said to be caused by the build-up of tangled clumps of a protein called “tau” in brain cells.
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.
In the study, the team examined the role played by the MARK4 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.
Problems start when a mutation occurs in the gene that provides the blueprint for making MARK4.
Previous work had already been linked to 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.
They found 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, but they also found that it aggregated much more easily and was 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 that involve the aggregation and buildup of other proteins.
The team says their insights into tau protein buildup may lead to new treatments and preventions for an even wider variety of neurodegenerative conditions.
If you care about Alzheimer’s disease, please read studies about the critical time window to stop Alzheimer’s disease, and why memory loss is an early symptom of Alzheimer’s.
For more information about brain health, please see recent studies about how BMI number affects the risk of Alzheimer’s disease, and results showing medical cannabis could help reduce this brain disease.
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