Grants and Contracts Details
Accumulating evidence suggests that the protein phosphatase, calcineurin (CN), plays a pathogenic role in several neurodegenerative diseases, including Alzheimer's disease (AD). In animal models of AD, commercially available CN inhibitors improve cognition, reduce neuroinflammation, and extend lifespan. Unfortunately, CN inhibitors also elicit numerous severe adverse effects, especially in elderly populations, forestalling their application to neurodegenerative diseases. To avoid these complications, our work has bypassed CN to focus instead on the CN-dependent transcription factor, NFAT. Using primary cell culture models of neuroinflammation and AD, we recently showed that astrocyte-specific inhibition of NFAT, with the peptide VIVIT, ameliorates neuronal dysfunction and excitotoxicity. My dissertation research will be the first to investigate the effects of astrocytic NFAT inhibition in an intact animal model of AD. I propose to use a novel adeno-associated virus to selectively deliver VIVIT to hippocampal astrocytes of transgenic mice expressing AD-like characteristics. Virus is delivered prior to the onset of pathology and cognitive deficits, and following treatment, AD biomarkers including amyloid deposition, neuroinflammation, synaptic dysfunction, glutamate dysregulation, and memory decline will be assessed using powerful multidisciplinary approaches. This work will greatly increase our understanding of CN/NFAT signaling in neurodegeneration and may lead to the development of more selective and efficacious treatments for AD.
|Effective start/end date||2/1/11 → 3/31/12|
- PhRMA Foundation: $25,000.00
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.