Metalloregulation of β-Amyloid

Amyloid Protein Structure

The β-Amyloid (Aβ) protein can aggregate to form fibrillar structures and plaques that are associated with the progression of Alzheimer's disease. The cupric ion, CuII, accelerates Aβ aggregation in vitro, and has been found at elevated concentrations in vivo in Alzheimer's plaques. Our aim is to understand the molecular mechanism of metal ion-mediated Aβ aggregation. The outcomes may lead to molecular therapeutic strategies for Alzheimer's disease, and other neurodegenerative diseases (for example, Parkinson's and Huntington's diseases, and prion-related diseases) that are associated with the accumulation of amyloid proteins. The results will also contribute to the characterization of amyloid structures (fibrils, sheets, tubes, spheres) as a nanomaterial.

In collaboration with Professor David Lynn (Department of Chemistry, Emory), we are studying the truncated Aβ(13-21) portion of the 42-amino acid human Aβ by using X-band continuous-wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopies. ESEEM of the CuII-amyloid complexes provides information about the number of histidine imidazole residues that coordinate the CuII.

Press release about our recent collaborative work:
http://news.emory.edu/Releases/Metals_to_Alzheimers1186774207.html

In collaboration with Professor Veronica Szalai (Department of Biochemistry, University of Maryland), we are applying EPR and ESEEM to determine the structure of CuII binding sites in full-length Aβ(1-40), and in smaller peptides.

We also are using ESEEM of different CuII-model complexes to determine the orientation of the histidine imidazole ligands in bis-histidine complexes.