Office of Undergraduate Research

The molecular basis of thymoquinone protection against beta-amyloid peptide toxicity

Beta-amyloid (Abeta) is central to Alzheimer's disease (AD) pathogenesis. Thymoquinone (TQ) has been shown to reduce Abeta toxicity in cell culture. However, the underlying molecular mechanisms remain unclear. The goal of this study is to explore the molecular basis of the observed TQ effect on Abeta toxicity. Abeta toxicity can be alleviated by enhancing Abeta clearance, inducing protective genes, or inhibiting pathogenic genes. Specifically, our objectives are (1) to determine the influence of TQ on gene expression changes known to play a role in AD pathogenesis and (2) to determine whether TQ treatment leads to enhanced clearance of Abeta. We will use real-time polymerase chain reaction to screen AD-related genes in the presence and absence of TQ to determine TQ effect on the expression of AD-related pathways. In addition, we will use immunohistochemistry to show Abeta levels in the presence and absence of TQ to determine whether it influences Abeta clearance.

Tasks and responsibilities:

Real-time PCR studies: The student will grow HT22 mouse hippocampal cells and treat them with Abeta alone or Abeta plus TQ. They will harvest the cells, extract RNA, synthesize cDNA, and perform real-time PCR. He will also be involved in data analysis and interpretation. Microscopy studies: The student will grow HT22 mouse hippocampal cells capable of expressing Abeta (which have been made by another undergraduate student in my lab), will treat these cells with TQ, stain treated and untreated cells with Abeta-specific antibodies, and compare treated versus untreated cells in terms of the amount of Abeta under either condition. The student will be required to write down the data in the form of a word document for possible future publication, and in the form of a poster to present on campus. The student will be provided with all necessary protocols, training, and guidance along the whole project.