Cleaning Toxic ‘Protein Clumps’ Could Prevent Dementia

The clean-up of cellular “protein clumps” can prevent the beginning of some forms of dementia, according to new research from The University of Queensland.

Scientists from the Queensland Brain Institute made the finding while emphasizing the relationship inbetween the enzyme Fyn and the protein Tau in frontotemporal dementia. The team, led by Dr. Ramón Martínez-Mármol and Professor Frederic Meunier, found that Fyn, a crucial participant in learning and memory, became highly active when it is paralyzed within the synapses which are the link hubs between neurons where neuronal communication takes place.

” Using super-resolution microscopy, we can currently see these enzymes independently and in real-time, moving arbitrarily in live neurons,” Lead author Dr. Martínez-Mármol claimed.

Protein clumps

The team discovered that when these enzymes become activated, they transform into an opened structure (like a flower that blooms) and reduce their movement, organizing with each other to make clusters or protein clumps before refolding and scattering to begin their cycle again.

” When they require to complete an action, the Fyn enzymes decrease and gather at the synapse to initiate their function,” Dr. Martínez-Mármol said.

Typically, this process happens naturally countless times at the synapses between neurons and is required to maintain neuronal communication, which is the foundation of learning and memory.

According to Professor Frederic Meunier, for learning and memory to occur, Fyn requires to form these dynamic clusters. “But if you alter the balance at all– you have insufficient or excessive clustering, you develop pathological issues,” he said.

Fyn and Tau enzymes

The study follows the group’s earlier job, where they discovered Tau affected a critical mechanism in memory function. The team revealed, using super-resolution microscopy, that when neurons are exposed to a mutant version of Tau existing in frontotemporal dementia, the clustering of Fyn enzyme is emphasized with the possibility of activating a debilitating chain reaction.

The association of Fyn and Tau needed for the development of different types of dementia, including Alzheimer’s disease and frontotemporal dementia, has been shown by numerous laboratories around the world; however, the exact molecular mechanisms behind this pathological interaction were unknown.

This mutant Tau has a greater propensity to form biomolecular condensates, which are small gel-like beads within the cells. Some proteins, under certain conditions, tend to spontaneously aggregate, developing droplets that appear like oil spills in an aqueous solution. Tau is just one of these proteins.

If formed at the neuronal synapses, these Tau beads produce the perfect trap for Fyn particles, keeping them immobile and accentuating their clustering and activation for longer.

New structures

“It is like a spider web,” Dr. Martínez-Mármol claimed. “Normally, Fyn moves and stops, moves and stops. In frontotemporal dementia, Fyn stops more as it gets stuck in this gel-like structure. The beads of Tau, for that reason, attract extra Fyn proteins at the synapse.”

Professor Meunier claimed Tau biomolecular condensates might hold the trick to reverting this poisonous chain reaction.

” We think they are the ideal target for future therapy to re-establish normal Fyn clustering dynamics,” Professor Meunier stated. “Theoretically, attacking the development of toxic Tau biomolecular condensates should prevent dementia from taking place.”

The research has been released in Molecular Psychiatry.

Read the original article on Medical Xpress.

Read more: Brain Cells on a Chip Discover to Play Pong within 5 Mins.