Tubulin prevents toxic protein clumps linked to neurodegeneration

Researchers at Baylor College of Medicine have discovered a potential new strategy to fight back against Alzheimer's and Parkinson's diseases, conditions that are linked to the toxic accumulation of Tau and alpha synuclein protein clumps in the brain. The team reports in Nature Communications that tubulin, the building block of microtubules, the cell's internal 'railway tracks,' can stop Tau and alpha synuclein from forming toxic clumps and instead steer them into their normal, healthy roles.

"Tau and alpha synuclein are well known for their roles in neurodegenerative diseases like Alzheimer's and Parkinson's. In these conditions, these proteins can misfold, stick together and form harmful aggregates that damage neurons and contribute to memory loss, movement problems and other symptoms," said first author Dr. Lathan Lucas, postdoctoral associate of biochemistry and molecular pharmacology in Dr. Allan Ferreon's lab. "But Tau and alpha synuclein also fulfill essential functions in healthy neurons – they help maintain cell structure and support communication by interacting with tubulin and contributing to microtubule assembly and stabilization."

To carry out their cellular functions, harmful or healthy, Tau and alpha synuclein concentrate inside tiny droplets, also called condensates. Although preventing the formation of these droplets is a potential therapeutic approach for neurodegenerative diseases, because such droplets also play healthy roles, their disruption could alter normal neuronal function.

"This led us to the following idea: what if instead of preventing the formation of droplets, we created conditions that would drive Tau and alpha synuclein inside the droplets toward their healthy path, discouraging them from taking the disease path?" said Ferreon, associate professor of biochemistry and molecular pharmacology and co-corresponding author of the work.