Fyn trajectories forming in a hippocampal dendritic spinal column. The cluster of Fyn is a crucial process of knowing and memory but when associated with Tau, can become the precursor to dementia. Importantly, this mutant Tau has a higher propensity to form what is known as biomolecular condensates, which are little gel-like droplets within the cells. Some proteins, under specific conditions, tend to spontaneously aggregate, forming droplets that resemble oil spills in an aqueous service. Tau is one of these proteins.
Dementia is a broad term that describes the impaired ability to keep in mind, believe, or make choices.
Sparking Learning and Memory
Recent research study from the University of Queensland suggests that clearing out cellular “protein clumps” may avoid the onset of certain forms of dementia.
The Queensland Brain Institute scientists made the finding after studying the link between the enzyme Fyn and the protein Tau in frontotemporal dementia.
The research team, led by Professor Frederic Meunier and Dr. Ramón Martnez-Mármol, found that Fyn, a key element of memory and knowing, ends up being extremely active when debilitated inside synapses, the connection centers between nerve cells where neuronal communication takes location.
” Using super-resolution microscopy, we can now see these enzymes individually and in real-time, walking around randomly in live neurons,” Lead author Dr. Martínez-Mármol said.
The research study group found that when these enzymes are activated, they change into an opened structure (comparable to a flower that blooms) and slow down their movement. They then cluster or form clumps of proteins before refolding and distributing to begin their cycle once again.
” When they require to complete an action, the Fyn enzymes slow down and gather together at the synapse to initiate their function,” Dr. Martínez-Mármol said.
Trajectory map of private Fyn particles in hippocampal neurons. Credit: Queensland Brain Institute
Protein clusters essential for finding out and memory
This procedure naturally happens countless times at the synapses in between nerve cells and is required to sustain neuronal interaction, which is the basis of knowing and memory. Teacher Frederic Meunier described that Fyn should form these vibrant clusters in order for learning and memory to happen.
” But if you alter the balance in any method– you have insufficient, or too much clustering, you establish pathological problems,” Professor Meunier said.
The research study follows the teams earlier work, where they found Tau affected a critical mechanism in memory function.
Fyn trajectories forming in a hippocampal dendritic spinal column. The cluster of Fyn is an important process of knowing and memory however when associated with Tau, can become the precursor to dementia. Credit: University of Queensland
The group revealed, utilizing super-resolution microscopy, that when nerve cells are exposed to a mutant version of Tau present in frontotemporal dementia, the clustering of the Fyn enzyme is emphasized with the prospective to set off an incapacitating chain response.
The association of Fyn and Tau necessary for the progression of various types of dementia, consisting of Alzheimers disease and frontotemporal dementia, has been shown by many labs around the globe; however, the exact molecular mechanisms behind this pathological interaction were not understood.
Hazardous Tau produces a dementia spider web
Significantly, this mutant Tau has a greater propensity to form what is called biomolecular condensates, which are small gel-like droplets within the cells. Some proteins, under specific conditions, tend to spontaneously aggregate, forming beads that resemble oil spills in a liquid solution. Tau is one of these proteins.
Dr. Ramón Martínez-Mármol. Credit: Queensland Brain Institute
If formed at the neuronal synapses, these Tau beads produce the ideal trap for Fyn particles, keeping them extremely immobile and highlighting their clustering and activation for longer.
” Its like a spider web,” Dr. Martínez-Mármol stated. “Normally, Fyn stops and moves, stops and moves
” In frontotemporal dementia, Fyn stops more as it ends up being stuck in this gel-like structure. The droplets of Tau, for that reason, attract additional Fyn proteins at the synapse.”
Professor Meunier stated Tau biomolecular condensates could hold the key to reverting this hazardous chain response.
” We believe they are the perfect target for future treatment to re-establish typical Fyn clustering characteristics,” Professor Meunier said.
” Theoretically, assaulting the formation of hazardous Tau biomolecular condensates need to prevent the procedure of dementia from occurring.”
Referral: “Fyn nanoclustering needs changing to an open conformation and is enhanced by FTLD-Tau biomolecular condensates” by Ramón Martínez-Mármol, Christopher Small, Anmin Jiang, Tishila Palliyaguru, Tristan P. Wallis, Rachel S. Gormal, Jean-Baptiste Sibarita, Jürgen Götz, and Frédéric A. Meunier, 18 October 2022, Molecular Psychiatry.DOI: 10.1038/ s41380-022-01825-y.
The study was funded by the National Health and Medical Research Council.
