Researchers at Baylor College of Medicine have identified a possible new way to address Alzheimer’s and Parkinson’s diseases. Their findings, published in Nature Communications, show that tubulin, a protein essential for the cell's internal structure, can prevent Tau and alpha synuclein from forming harmful clumps linked to these neurodegenerative conditions.
“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.”
The researchers explained that both Tau and alpha synuclein concentrate inside small droplets within cells. These droplets can be involved in both normal cellular processes as well as disease pathways. While stopping the formation of these droplets might seem like a solution for preventing disease, doing so could disrupt important healthy functions.
“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.
“I think of Tau and alpha synuclein as troublemaker kids in school. You can keep them in the classroom with little to do but to act out or keep them engaged with schoolwork, sports or theater so they do not get in trouble,” Lucas said. “We found that tubulin can drive Tau and alpha synuclein troublemakers down a healthy path.”
Using biochemical techniques, microscopy, and neuron-based tests, the team studied how tubulin influences whether these proteins become toxic or remain beneficial.
“When tubulin levels are low, as it has been found in Alzheimer’s disease, microtubules are less abundant and Tau and alpha synuclein can form toxic aggregates,” Lucas said. “But when tubulin is present, Tau and alpha‑synuclein shift away from harmful aggregates and instead promote the assembly of healthy microtubules,” Lucas said. “Tubulin redirects the activity of these proteins by giving them something productive to do.”
“Our findings significantly shift tubulin's role in neurodegeneration, from a passive casualty of disease to an active protector against toxic protein aggregation,” Ferreon said. “Boosting the tubulin pool, rather than blocking droplet formation, can curb toxic aggregation while preserving the healthy roles of Tau and alpha synuclein, offering a potential selective therapeutic strategy.”
Other contributors include Phoebe S. Tsoi (co-first author), My Diem Quan, Kyoung-Jae Choi, and Josephine C. Ferreon (co-corresponding author), all affiliated with Baylor College of Medicine.
Baylor College of Medicine is an independent health sciences university focused on research advancement, education across its schools, patient care through partnerships with clinical institutions such as hospitals or clinics [source], community service [source], biomedical research [source], integrated health sciences environments [source], as well as providing leadership under Paul Klotman who serves as president [source].
The study was funded by grants from NINDS-NIH (R01 NS105874), Welch Foundation (Q-2097-20220331), and NIGMS-NIH (R01 GM122763).
