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Home / Health / The cause of Alzheimer’s disease is derived from a genetic mutation in a common enzyme

The cause of Alzheimer’s disease is derived from a genetic mutation in a common enzyme



MARK4 Mutation Causes Alzheimer's Disease

The mutant MARK4 produces a form of tau that easily accumulates in brain cells, causing nerve cell death. Credit: Tokyo Metropolitan University

A mutation into MARK4 causes proteins to stick more tightly and are more likely to accumulate in the brain.

Researchers from Tokyo Metropolitan University have discovered a new mechanism by which tau protein blocks are created in the brain, killing brain cells and inducing Alzheimer sick. A specific mutation for an enzyme called MARK4 changes the properties of tau, which is often an important part of a cell’s skeletal structure, making it more likely to agglomerate and difficult to dissolve. than. Understanding mechanisms like these can lead to breakthrough treatments.

Alzheimer’s disease is a debilitating, life-changing condition that affects tens of millions of people worldwide. According to the World Health Organization, it is the most common cause of senile dementia, with the number worldwide expected to double every 20 years if left unchecked.

Alzheimer’s disease is thought to be caused by an accumulation of tangles of a protein called “tau” in brain cells. These adhesions cause nerve cells to die, leading to impaired memory and motor functions. It is still unclear how and why tau accumulates in the brain cells of Alzheimer’s patients. Understanding the causes and mechanisms behind this unwanted clumping will open up new treatment directions and ways to prevent the disease.

A research team led by Associate Professor Kanae Ando of Tokyo Metropolitan University has explored the role of the enzyme MARK4 (Kinase 4 microtubular affinity regulation) in Alzheimer’s disease. When everything is working properly, the tau protein is an important part of the cell’s structure, also known as the cell skeleton. To keep the arms of the skeleton either micro tube Continuously build and disassemble, MARK4 really helps me to separate from the branches of this structure.

Problems begin when a mutation occurs in a gene that provides blueprints for creating MARK4. Previous studies have linked this with an increased risk of Alzheimer’s disease, but it is not known why. The team artificially inserted the mutations into the gene transfer drosophila Fruit flies also create tau for humans and study how proteins are changed in vivo. They found that this type of MARK4 mutation induces changes to the tau protein, creating a pathological form of tau. Not only does this “bad” tau have an excess of certain chemical groups causing it to degrade incorrectly, they also find that it agglomerate much easier and no longer dissolves in detergent. This makes it easier for tau to form tangles that degrade nerve cells.

MARK4 has also been found to cause many other diseases involving the combination and accumulation of other proteins. That is why the group’s insights into tau protein accumulation could lead to new treatments and preventive measures for many types of neurodegenerative diseases.

Reference: “Kinase 4 microtubular affinity regulation with Alzheimer’s-related mutations promotes tau accumulation and aggravates neurodegeneration” by Toshiya Oba, Taro Saito, Akiko Asada, Sawako Shimizu, Koichi M Iijima and Kanae Ando, ​​October 5, 2020, Journal of Biological Chemistry.
DOI:

This work is supported by the Scientific Research Support Organization of the Creative Fields (Controlling Protein Aging in the Brain and Dementia) [JSPS KAKENHI Grant number 17H05703], a research award from the Hoan-sha Foundation, the Takeda Science Foundation, a research award from the Japan Health and Aging Foundation, and a Scientific Research grant for a Challenge (Discovery) study. [JSPS KAKENHI Grant number 19K21593], and the 19-7 Life Science Research Foundation from the National Center for Geriatrics and Geriatrics, Japan.




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