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Research Grants 2010

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

2010 Grants - Jinwal

Behavioral and Biochemical Analysis of Mice Lacking FKBP51

Umesh Kumar Jinwal, Ph.D.
University of South Florida
Tampa, Florida

2010 New Investigator Research Grant

The protein tau normally plays an important role in maintaining the structure of brain cells. Tau is usually modified in a process called phosphorylation, or the addition of phosphate molecules. During Alzheimer's disease, however, tau becomes excessively phosphorylated and loses its ability to carry out normal functions. This hyperphosphorylated tau tends to accumulate into harmful clumps called neurofibrillary tangles, a key hallmark of Alzheimer's.

Umesh Kumar Jinwal, Ph.D., and colleagues have studied a protein called FKBP51, which acts as a chaperone for tau. Chaperones help other proteins assume their correct shape. The researchers observed that FKBP51 may help modify tau phosphorylation and prevent the clearance of abnormal tau from brain cells. They also found that mice engineered to lack FKBP51 had reduced levels of tau compared to normal mice. Both findings indicate a role for this chaperone in the production of hyperphosphorylated tau—and the accumulation of tau—in Alzheimer's disease.

For their proposed grant, the researchers will study the effects of genetically deleting FKBP51 in normal mice and in mice bred to develop Alzheimer-like pathologies. They will assess whether eliminating FKBP51 in normal mice alters the production of normal tau and leads to behavioral changes. The researchers will then analyze whether knocking out the chaperone in Alzheimer-like mice can ameliorate the animals' tau-related pathologies and behavioral problems.

Results of this study could shed new light on how tau exerts its toxicity in Alzheimer's disease. Moreover, the researchers hope their study will lead to further research on disease-associated chaperone proteins.

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

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