Deguo Du, Ph.D. , an associate professor in the Department of Chemistry and Biochemistry, and collaborators, were awarded a National Institute of Health (NIH) grant of $444,434 for the research project titled “Role of the N-terminal Region in Abeta Oligomer and Fibril Formation.” This project involves the investigation of Alzheimer’s disease and the fundamental reasons for the development of this disease. Numerous evidence points to the accumulation of a specific peptide, called amyloid-β (Aβ), which causes neuronal death that leads to cognitive decline. However, the exact mechanism by which Aβ causes neuronal death still remains mysterious.
Du and collaborators are looking to better understand Aβ self-assembly at the membrane interface, and the molecular mechanisms of Aβ-induced membrane damage which may cause neuronal death. Deguo Du explains, “We are performing systematic mutagenesis studies targeting the specific key residues/sequence regions, including those involved in mutagenesis in familial Alzheimer’s disease (FAD), and hope to identify the critical interactions that play a dominating role in Aβ–membrane binding, membrane-mediated Aβ self-assembly, and Aβ-induced membrane disruption.”
A combination of biophysical and biochemical approaches will be utilized in this study. The correlation of the Aβ-induced membrane permeation and disruption, membrane oxidation, and the cellular toxicity, will also be carefully investigated. The knowledge from this research may also facilitate the identification of novel molecular targets of the key local residues/regions of Aβ for design of strategies to manipulate Aβ self-assembly in vivo, which may lead to the development of new therapeutic treatment for Alzheimer’s disease.