Researchers at Baylor College of Medicine report that tubulin—the building block of microtubules—can shift Tau and alpha-synuclein inside cellular condensates away from disease-linked aggregation and toward roles that support healthy neurons.
Scientists at Baylor College of Medicine say they have identified a possible new strategy for addressing processes linked to Alzheimer’s and Parkinson’s diseases, both of which are associated with harmful clumps of the proteins Tau and alpha-synuclein in the brain.
In a study published in Nature Communications, the researchers report that tubulin, a protein that forms the building blocks of microtubules, can reduce the tendency of Tau and alpha-synuclein to form damaging aggregates. Instead, tubulin appears to push the proteins toward activities tied to normal cell function, including microtubule assembly and stabilization.
“Tau and alpha-synuclein are well known for their roles in neurodegenerative diseases like Alzheimer’s and Parkinson’s,” said first author Dr. Lathan Lucas, a postdoctoral associate in Dr. Allan Ferreon’s lab, in a Baylor statement carried by ScienceDaily. Lucas added that when tubulin levels are low—something the researchers said has been reported in Alzheimer’s disease—microtubules are less abundant and the proteins can form toxic aggregates.
The team framed the work as an alternative to approaches aimed at preventing the formation of condensates—tiny droplets in cells where the proteins can carry out both healthy and harmful activities—because condensates also have important roles in normal cell biology.
“Our findings significantly shift tubulin's role in neurodegeneration, from a passive casualty of disease to an active protector against toxic protein aggregation,” Ferreon, an associate professor and co-corresponding author, said in the same statement. He added that increasing the available tubulin pool, rather than blocking droplet formation, could potentially curb toxic aggregation while preserving the proteins’ normal roles.
Other contributors listed by the research organization include co-first author Phoebe S. Tsoi, My Diem Quan, Kyoung-Jae Choi, and co-corresponding author Josephine C. Ferreon.
The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health under grant R01 NS105874, the Welch Foundation under grant Q-2097-20220331, and the National Institute of General Medical Sciences (NIGMS) at the NIH under grant R01 GM122763.
