Grants and Contracts Details
Alzheimer's disease (AD), the sixth leading cause of death in the US, is characterized in part by the deposition of neurofibrillary tangles in effected brain tissue. Tangles result from aggregation of hyperphosphorylated forms of the microtubule-binding protein tau. The origins of tau hyperphosphorylation are currently unknown, but likely involve increases in kinase activity, decreases in phosphatase activity, or a combination of the two. Calcineurin (CaN) dephosphorylates seven of 85 possible sites of phosphorylation in tau. This phosphatase is of critical importance because it acts upon the residues T231 and S262 which are known to be important for regulation of tau binding to microtubules. Phosphorylations at T231 and S262 are also involved in the early stages of tau pathology, and prime further phosphorylation events within tau. The goal of this proposal is to gather the preliminary data necessary for more detailed future investigations of the role of CaN plays in regulating the microtubule-binding function of tau. How CaN recognizes and binds to tau is not known. In this work we will identify the CaN binding sites within tau. Biochemical assays and biophysical techniques, primarily fluorescence-based, will be employed. Data collected will be used in a NIH R01 proposal on investigations of the role of CaN plays in regulating tau function, and how disruption of that regulation leads to hyperphosphorylation and the subsequent formation of neurofibrillary tangles in AD.
|Effective start/end date||7/1/15 → 6/30/17|
- KY Science and Technology Co Inc: $30,000.00
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