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Research Grants 2013

To view an abstract, select an author from the vertical list on the left.

2013 Grants - Southworth

Molecular Chaperone Quality Control Mechanisms of Tau Regulation in Alzheimer's Disease

Daniel R. Southworth, Ph.D.
University of Michigan
Ann Arbor, Michigan

2013 New Investigator Research Grant

Tau is a protein that normally functions in helping maintain cell structure and in transporting nutrients throughout the cell. In people with Alzheimer's disease, tau in the brain becomes abnormal, forming neurofibrillary tangles, one of the characteristic features of Alzheimer's disease.

In healthy cells, the tau protein is folded into its correct shape with the help of three other proteins, known as molecular chaperones. These three proteins — known as HSP70, HSP90 and CHIP — also help to recognize abnormal copies of tau, directing the cell to dispose of those copies. There is evidence that, in Alzheimer's disease, those molecular chaperones become overwhelmed by abnormal tau, allowing it to accumulate into neurofibrillary tangles.

Daniel R. Southworth, Ph.D., and colleagues have proposed to study the precise molecular interactions between tau and its molecular chaperones. These interactions can occur rapidly and change over time, ruling out the use of traditional methods for studying protein structure. Instead, Dr. Southworth's team will use a technique called cryo-electron microscopy, which involves rapid freezing of tau and its chaperones as they interact, followed by high-resolution electron microscopy. The researchers will use this method to describe the 3-dimensional structure of the protein complex formed by tau and its chaperones. They also intend to determine how the chaperones recognize abnormal tau and direct the cell to dispose of it. These studies may yield important clues about ways to prevent the accumulation of abnormal tau in Alzheimer's disease, potentially slowing or halting disease progression.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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