Understanding protection from AD by non-steroidal anti-inflammatory drugs

Thomas Kukar, PhD
Mayo Clinic Jacksonville (Jacksonville, FL)

Mentors

Todd Golde, M.D., Ph.D.
Mayo Clinic Jacksonville
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2009
Disease:
Alzheimer's Disease
Award Amount:
$100,000
Grant Reference ID:
A2007623
Award Type:
Postdoctoral Fellowship
Award Region:
US Southeastern

Anti-Amyloid Effects of Truncated Abeta Peptides

Summary

Studies have shown that Aß42 is much more prone to form amyloid than shorter fragments. Based on these results, we hypothesized that the elevations in shorter Aß peptides induced by some NSAIDs further enhances their anti-amyloidogenic effect. Experiments will directly investigate the effects of smaller Aß peptides on Aß aggregation and fibril formation in vitro.

Details

Understanding the factors responsible for Alzheimer's disease (AD) is critical for the development of therapeutic strategies for this debilitating neurodegenerative disease. Intriguingly, epidemiological studies suggest that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) protects from the development of AD. We have shown that certain NSAIDs selectively lower production of the 42 amino acid form of the amyloid beta peptide (Aß42). Based on evidence that the accumulation of Aß42 in the brain leads to AD, it has been hypothesized that this unique property may contribute to the protective effect of some NSAIDs. These compounds not only selective lower Aß42 but also increase the levels of shorter Aß peptides such as Aß34, 37, and 38. Studies have shown that Aß42 is much more prone to form amyloid than shorter fragments. Based on these results, we hypothesized that the elevations in shorter Aß peptides induced by some NSAIDs further enhances their anti-amyloidogenic effect. Experiments will directly investigate the effects of smaller Aß peptides on Aß aggregation and fibril formation in vitro. Most importantly a unique technology to rapidly and specifically increase the levels of these short Aß peptides in the brains of mice will be used to see if they protect from Aß plaque formation.
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