Neuroprotective Effects of Selective Estrogen Receptor Modulators Against Amyloid Beta Toxicity and the Pathways That Provide Protection

Abstract

Alzheimer's disease is the sixth leading cause of death in the United States. The leading hypothesis to explain the prevalence of the disease in the brain is the aggregation of Amyloid Beta peptides in the brain, which form senile plaques and suppress neuronal function. Selective estrogen receptor modulators (SERMs) have been found to provide protective effects against the neurotoxic effects of Amyloid Beta. This experiment was conducted in two distinct phases: the experimental phase and the literature review phase. The experimental phase sought to determine if Amyloid Beta was neurotoxic to SH-SY5Y neuroblastoma cells, and if STX-an SERM-was able to rescue cell viability after exposure to Amyloid Beta toxicity. During the literature review phase, potential pathways already described in the literature were identified, which might be able to account for how STX was able to rescue cell viability after exposure to Amyloid Beta toxicity. Amyloid Beta was found to have a significant toxic effect on cell viability when compared to a control assay of cells grown in DMSO. STX, however, was not found to have a significant rescue effect against Amyloid Beta toxicity. The literature review identified several pathways that were likely candidates for neuroprotection, including MAPK, ERK1, ERK2, and PI3K. The future direction of this experiment would be to determine if STX is as effective at providing neuroprotection against Amyloid Beta as previously suggested by similar experiments. the next stage of investigation would then be to inhibit different pathways that have been identified as possible pathways for neuroprotection.