Researchers at Baylor College of Medicine have identified a new approach that could help address Alzheimer's and Parkinson's diseases by focusing on the role of tubulin, a protein essential for cell structure. Their findings were published in Nature Communications.
The study examined how Tau and alpha synuclein proteins, which are linked to neurodegenerative diseases when they form toxic clumps, can be influenced by tubulin. Dr. Lathan Lucas, postdoctoral associate in Dr. Allan Ferreon's lab and first author of the study, explained: "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." He added that both proteins also play important roles in healthy neurons by interacting with tubulin to support microtubule assembly.
The research team explored whether encouraging Tau and alpha synuclein to follow their normal cellular functions—rather than preventing them from forming droplets entirely—could reduce disease risk without interfering with healthy neuron activity. Dr. Allan Ferreon said: "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?"
Using various laboratory techniques including high-resolution microscopy and neuronal-based assays, the researchers found that low levels of tubulin—as observed in Alzheimer's disease—are associated with fewer microtubules and more toxic protein aggregates. Lucas stated: "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," adding: "But when tubulin is present, Tau and alpha‑synuclein shift away from harmful aggregates and instead promote the assembly of healthy microtubules. Tubulin redirects the activity of these proteins by giving them something productive to do."
Ferreon highlighted the significance of this discovery: "Our findings significantly shift tubulin's role in neurodegeneration, from a passive casualty of disease to an active protector against toxic protein aggregation," he 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 included 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.
The research received funding from NINDS-NIH grant R01 NS105874; Welch Foundation grant Q-2097-20220331; and NIGMS-NIH grant R01 GM122763.
