Exploring Mechanisms of Neuroserpin Regulation in Alzheimer's Disease

Researchers: 
Funding year(s): 
2010 - 2011
Funding to date: 
$100,000

Understanding the up-regulation of Neurosperpin in Alzheimer’s disease brain and isolating a potential therapeutic inhibitor of its action; a continuation.

Specific aim #1 for the project is to determine what is responsible for the up-regulation of neuroserpin in the Alzheimer’s disease brain? 

Specific aim #2for the project is to use a sensitive high throughput assay screen for inhibitors of Neuroserpin to:

  1. Screen commercially available libraries and selected chemical compounds.
  2. b. Use medicinal chemistry to optimize and design new molecules based on the structures of identified hit candidate molecules (above) and crystal structure of neuroserpin.
  3. Confirmation of screening “hits”:  rule out false positives, do dose response curves and counter-screens to identify “leads”.
  4.  Test for “hit” interaction with neuroserpin, possible mechanism of action and potential toxicity in hippocampal neuronal cell cultures.