Tau, the "other" protein that goes awry in Alzheimer's disease (beta-amyloid being the best-known), is enjoying a resurging interest among researchers. Contributing to the renewed interest in tau is a growing recognition of its important role not just in Alzheimer's but in other neurodegenerative diseases as well, including Parkinson's, frontotemporal dementia, and Pick's disease-what are collectively called tauopathies.
Tau normally functions as scaffolding for microtubules, structures within the cell that act like railroad tracks to transport molecules from one part of the cell to another. In tauopathies, tau accumulates abnormally, tangling up the microtubules and causing a traffic jam among the enzymes and phosphates that cell physiology requires to keep chugging along.
What drives the buildup of tau is a critical question, one likely to have many answers. In Alzheimer's, for example, beta-amyloid seems to trigger tau aggregation; in Parkinson's, a protein called alpha-synuclein does. Tau may represent "a final common pathway by which neurons die" in a number of pathologic conditions, according to Virginia M-Y Lee, a neuroscientist at the University of Pennsylvania.
"When overexpressed, tau, by itself, kills neurons," Lee said. "So if you can impact tau, you can potentially address all these different diseases." Her laboratory is among those trying to identify drugs that can stabilize microtubules and cross the blood-brain barrier to act on neurons. The anticancer drug paclitaxel, or Taxol, has proved effective. Lithium, a drug used for some neuropsychiatric disorders, inhibits tau formation in cultured cells, and a clinical trial investigating it in mild cognitive impairment is slated to begin next year.