As of 2017, 5.5 million Americans were diagnosed with Alzheimer’s disease (AD); the sixth leading cause of death in the United States. Researchers today look to either prevent or slow the progression of AD and one potential treatment is with highly selective calpain inhibitors. Calpain, a protease enzyme, assists in the observed neurodegeneration associated with AD by regulating proteins that are essential for Alzheimer’s. These highly selective calpain inhibitors are necessary to prevent negative side effects, which can include immunosuppression from cathepsin, another protease. A recent study by Kling et al looked at potential calpain inhibitors and used a variety of experiments to determine their inhibitory efficacy. This study will look at those inhibitors using molecular dynamics to assess their viability as an inhibitor. Promising potential inhibitors from the ZINC Fragments database (Figure 1) were docked, analyzed, and compared to the standards established by Kling et al. Preliminary results suggest that the standard calpain inhibitors are following the trends demonstrated by Kling et al, yet more testing is required for using these inhibitors as standards. MD and analysis on the potential ZINC inhibitors is ongoing. These results will hopefully aid in discovering more viable calpain inhibitor treatments for Alzheimer’s patients.

Determining the viability of calpain inhibitors as drugs for Alzheimer's disease

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.