Dementia could be prevented by restoring and normalizing protein clusters

Toxic protein clumps known as Fyn are causing dementia in people due to changes in the protein.
Brittney Grimes
Synapse of connected neurons concept image.
Synapse of connected neurons concept image.

koto_feja/iStock 

Dementia is a disease that impairs memory and decision-making skills. The clean-up of toxic protein clumps could prevent neurodegenerative diseases, according to a new study.

The study was led by researchers from the Queensland Brain Institute. The research team discovered that focusing on the relationship between two key enzymes could prevent dementia. The proteins the researchers studied were the enzyme Fyn and the protein Tau. They studied the area of the brain that causes frontotemporal dementia, a form of brain disorder that forms when parts of the frontal and temporal lobes are damaged, affecting behavior, language and movement.

The study was published in the journal Molecular Psychiatry.

The research team was led by Professor Frederic Meunier and Dr. Ramón Martínez-Mármol of the Queensland Brain Institute. Researchers found that Fyn, an enzyme that plays a significant role in learning and memory, became active when it was immobilized within the synapses – a link between two nerve cells – that connected hubs between neurons, where the enzymes normally communicate.

“Using super-resolution microscopy, we can now see these enzymes individually and in real-time, moving around randomly in live neurons,” said Dr Martínez-Mármol, lead author on the study.

The protein clumps and the cyclic process

Overall, the team discovered that the enzymes changed into an opened structure, like a blossoming flower, when the enzymes are activated. The enezymes also slow down their movement and group together to form the clusters, or clumps, of protein. Then, they fold back into each other and disperse, repeating the cycle over again.

“When they need to complete an action, the Fyn enzymes slow down and congregate at the synapse to initiate their function,” Dr. Martínez-Mármol said.

Typically, the process happens automatically thousands of times at the synapses between the nerve cells. It is usually a normal process that is considered essential so that the neurons can communicate. This is the basis of memory and learning.

As explained by Meunier, the Fyn enzymes are needed so that learning, understanding and recollection can happen. However, there can be issues if the clustering isn’t the correct, balanced amount, as mentioned by Professor Meunier. “If you alter the balance in any way – you have too little, or too much clustering, you develop pathological issues,” Meunier said.

Tau and the impact on memory

The research team mentioned their prior work, which was the preliminary study of how Tau impacted an important process of memory and the protein’s function. The researchers used a type of microscopy called super-resolution microscopy.

This showed that when the neurons were exposed to a mutant version of the protein Tau present in the frontotemporal dementia, the clustering of the Fyn enzyme is heightened, leading to a devastating chain reaction and causing dementia. The researchers found out how Fyn and Tau cause the progression of different types of dementia, more specifically, which molecular mechanisms were exactly behind the interactions of proteins. The study also stated that the altered version of Tau has a higher predisposition to forming ‘biomolecular condensates’, which are small gel-like droplets within the cells. Some proteins, such as Tau, also accumulate and form droplets that look like oil spills in water.

“In frontotemporal dementia, Fyn stops more as it becomes stuck in this gel-like structure. The droplets of Tau, therefore, attract additional Fyn proteins at the synapse.”

Meunier mentioned that Tau enzymes could hold the key to reverting this toxic chain reaction with Fyn proteins.

“We believe they are the perfect target for future therapy to re-establish normal Fyn clustering dynamics,” Meunier said.

message circleSHOW COMMENT (1)chevron