The mutant MARK4 creates a form of tau which accumulates easily in brain cells, causing neurons to die.
CREDIT: Tokyo Metropolitan University
Mutation to MARK4 makes proteins stickier and more likely to clump in brain
Researchers from Tokyo Metropolitan University have discovered 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.
Alzheimer’s disease is a life-changing, debilitating condition, affecting tens of millions of people worldwide. According to the World Health Organization, it is the most common cause of senile dementia, with numbers worldwide expected to double every 20 years if left unchecked.
Alzheimer’s 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. Understanding the cause and mechanism behind this unwanted clumping would open up the way to new treatments and ways to prevent the disease.
A team led by Associate Professor Kanae Ando of Tokyo Metropolitan University 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.
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 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 causes 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 buildup may lead to new treatments and preventative measures for an even wider variety of neurodegenerative conditions.
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
Tau protein buildup
- More Evidence that Locus Coeruleus Demise Precedes Cortical Tangles
Transcriptomics hinted that dysfunctional intracellular protein transport might explain susceptibility ... To look for direct evidence that tau deposits in the LC first, Bueichekú and colleagues ...
- A Common Sleeping Pill May Reduce Build-Up of Alzheimer's Proteins, Study Finds
There's still so much we don't know about Alzheimer's disease, but the link between poor sleep and worsening disease is one that researchers are exploring with gusto.
- Youth-Onset Diabetes Linked to Higher Alzheimer’s Risk
The study discovered blood biomarkers and amyloid protein accumulations typical of AD in individuals diagnosed with diabetes during childhood or adolescence.
- Stopping Alzheimer’s Before Symptoms Appear
tackling the tangles of tau protein that form in the brains of Alzheimer’s patients around the time symptoms emerge. One theory gaining prominence in the field is that the long buildup of plaque ...
- Scientists reveal nanoparticle that can treat Alzheimer’s disease in mice
Researchers say a promising new therapy targets protein clusters that likely cause neuron death and brain atrophy in Alzheimer’s disease.
Go deeper with Google Headlines on:
Tau protein buildup
[google_news title=”” keyword=”tau protein buildup” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
Go deeper with Bing News on:
MARK4 enzyme
- 5 Ways to Use Papain
Papain is an enzyme found in papaya, but it’s also available in other forms. Limited research suggests it may offer some health benefits, like improved digestion. Papain is a proteolytic enzyme ...
- What Are High ALT Levels and How to Lower Them
A liver enzyme known as ALT plays an important role in breaking down proteins in the digestive process. High levels of ALT in the blood can indicate liver issues. Implementing these strategies may ...
- Top 5 Best Enzyme Supplements in 2024
The overall well-being of our body is heavily reliant on enzymes. These vital components transform food into nutrients that our body can use. Nonetheless, there might be individuals who naturally ...
- What to know about cardiac enzymes (cardiac biomarkers)
Elevated cardiac enzyme levels indicate when someone has experienced a heart attack. A cardiac enzyme test can measure the amount of cardiac enzymes in a person’s blood. Certain enzymes are ...
- Top 9 Best Digestive Enzyme Supplements in 2024
The importance of a healthy gut for overall well-being cannot be overstated, made evident by the rising popularity of digestive enzyme supplements. These supplements include a critical mix of ...
Go deeper with Google Headlines on:
MARK4 enzyme
[google_news title=”” keyword=”MARK4 enzyme” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
