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2016 Grants - Shahpasand
Reason of Tau Toxicity Upon Cistauosis
Koorosh Shahpasand, Ph.D.
Royan Institute for Stem Cell Biology and Technology
2016 New Investigator Research Grant
How does an abnormally modified version of the tau protein promote nerve cell death?
Tau is a protein that normally functions to transport nutrients and help nerve cells maintain their proper structure. In Alzheimer’s and other neurodegenerative diseases, tau protein can become abnormally modified by the addition of phosphate molecules. A specific phosphate-modified version of tau protein, called “cis P-tau,” can be found in the brains of mice just hours after a traumatic brain injury. Cis P-tau is also found in the brains of people with Alzheimer’s disease. It is hypothesized that this modified tau protein disrupts nerve cell structure and nutrient transport, leading to nerve cell death. While cis P-tau appears to be a major contributor to the harmful effects of tau accumulation in the brain, the mechanisms underlying its toxicity are not yet understood.
Dr. Shahpasand, Ph.D. and colleagues have proposed a series of studies to better understand the mechanisms of cis P-tau toxicity in the brain. In initial experiments, the researchers found that when cis P-tau was transported from the outside of a nerve cell to its nucleus it had particularly toxic effects. The nucleus of a cell is a specialized structure that houses the cell’s genetic material (DNA) and controls many important cell functions. For their current studies, Dr. Shahpasand’s team will use nerve cells growing in laboratory dish to study the molecular mechanisms by which cis P-tau is transported to the nucleus. The researchers will also examine how cis P-tau affects the function of the nucleus and determine if it has harmful effects on the DNA.
The results of these studies may shed new light on the toxic effects of abnormally modified tau protein. Because the activity of cis P-tau is thought to be one of the earliest steps linked with development of brain changes related to Alzheimer’s disease, understanding the mechanisms of cis P-tau toxicity may help scientists develop new ways to slow or halt the disease.