Many aspects of Alzheimer’s disease remain a mystery, but scientists know that the disease’s progression involves the tau protein. In Alzheimer’s, the tau protein clumps together to form rope-like inclusions in brain cells that eventually strangle neurons. What has not been known until now is how the protein transitions from its liquid state to solid fibers.
Researchers have discovered a property of tau that helps explain how the protein can change from liquid to solid state. When tau is in a complex with RNA, it can condense into a compact “droplet”. During a process called phase separation, tau and RNA hold together without a membrane, but remain separate from the surrounding milieu, leading to highly concentrated tau that becomes vulnerable to aggregation.
The research demonstrated that up to eight tau molecules bind to the RNA, forming an extended fluidic assembly. Other proteins similar to tau also irreversibly aggregate in other neurodegenerative diseases, such as ALS, also known as Lou Gehrig’s disease.
Researchers plan to search for the counterpart of tau droplets in living cells. They will also study why and how cells regulate the formation of the droplets, and whether this could represent a possible path toward therapy.
Paper: “Neurodegenerative diseases: A biophysical smoking gun: Scientists begin to unravel how the protein tau transitions from a soluble liquid state to solid fibrous tangles”
Reprinted from materials provided by University of California – Santa Barbara.