Sticky Alzheimer's
Alzheimer's disease linked to sticky mutant protein
Japanese scientists have discovered that a mutation in the gene of the protein MARK4 (microtubule-affinity regulating kinase 4) makes its structure more sticky and, therefore, it is more likely to accumulate in the brain. This eventually leads to Alzheimer's disease. The discovery is described in the Journal of Biological Chemistry (Oba et al., Microtubule Affinity Regulating Kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and excerbates neurodegeneration).
Today, tens of millions of people around the world suffer from Alzheimer's disease. According to the World Health Organization, it is currently the most common cause of senile dementia. It is expected that if an effective cure for this disease is not found in the near future, the number of cases worldwide will double every 20 years.
It is believed that Alzheimer's disease is caused by the accumulation and formation of large clots of tau protein in the brain. These sticky aggregates cause the death of neurons, which leads to memory impairment, impaired motor functions, and subsequently to the death of a person. To date, the exact reason why tau protein suddenly begins to accumulate in the cells of patients with Alzheimer's disease has not been established. A detailed understanding of the mechanisms of the formation of this "cellular debris" can help in the development of new methods of treatment and prevention of the development of the disease.
Researchers from The University of Tokyo, led by associate Professor Kanae Ando, discovered the probable cause of the development of a pathological brain condition that is usually associated with the development of Alzheimer's disease. They studied the role played by the enzyme MARK4 (kinase 4, which regulates affinity for microtubules) in the development of the disease. Normally, tau protein is an important part of the cell structure and its cytoskeleton. In order for the end sections of microtubules to be constantly disassembled and re-aligned, it is necessary that the tau protein detaches from them in time. It is the MARK4 enzyme that helps the tau protein do this.
However, if the gene that creates the normal MARK4 protein carries a mutation, problems begin. Scientists were able to make point changes to the genome of transgenic fruit flies, which, among other things, produces human tau protein. As a result, it was possible to trace in vivo how the broken MARK4 enzyme makes changes in the work of the tau protein, creating its pathological form.
Figures from the article by Oba et al.
Under the influence of the mutant form of MARK4, an excessive amount of certain chemical groups (phosphoric acid residues) appears on the tau protein, which causes it to collapse into an irregular shape. This "bad" tau protein accumulates much more easily in the form of dense clots, can no longer be dissolved by detergent substances and as a result causes neurodegeneration.
The degree of aggregation of tau protein in the conjugated expression of various types of damaged enzyme MARK4.
The researchers also found that breakdowns in the MARK4 enzyme gene can cause a fairly wide range of other diseases that are associated with the accumulation and aggregation of other proteins inside nerve cells. That is why studies of this protein and its interactions with cellular structures will help in the development of new treatments for a wide range of neurodegenerative diseases.
Portal "Eternal youth" http://vechnayamolodost.ru