Inhibition of Amyloid Protein Aggregation

Professor Yan Sun, Department of Biochemical Engineering
School of Chemical Engineering and Technology
Tianjin University, Tianjin

Inhibition of Amyloid Protein Aggregation 

A nascent protein (peptide) needs to fold to its specific tertiary structure to function in a living system, so how a protein folds is an essential issue of life science studies. If a protein fails to fold correctly or protein misfolding occurs in vivo, the misfolded protein will accumulate and aggregate in the living system, resulting in serious diseases. Currently, over 50 diseases have been identified to be related to in vivo protein misfolding and aggregation, including neurodegenerative diseases (e.g., Alzheimer’s disease, AD), metabolic diseases and cancers. Hence, inhibition of in vivo protein aggregation is a major concern in medical science. This presentation will describe our efforts on the discovery and design of new inhibitors against amyloid b-protein (Ab) aggregation (fibrillogenesis) as well as metal (Zn²⁺ and Cu²⁺)-mediated Aβ aggregation, which have been recognized as the main hallmark of AD.

Firstly, we discovered a natural compound (brazilin) that inhibits Ab fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity. Secondly, we proposed to modify serum albumin to explore protein-based Ab aggregation inhibitors. Results revealed that acidulated human serum albumin (HSA) showed significantly higher inhibitory effects than native albumin, and a hydrophobic binding-electrostatic repulsion (HyBER) hypothesis was proposed to explain the phenomenon. Moreover, we succeeded in functionalizing HSA with iminodiacetic acid to create a multifunctional agent for inhibiting high-concentration metal-induced Aβ aggregation and remodeling mature metal-induced Aβ species. Thirdly, we have designed new peptide inhibitors and developed different peptide-nanoparticle conjugates and self-assembled nano-conjugates by incorporating peptide or small molecular inhibitors into nanoparticles or natural polymers. It was interesting to note that the nano-inhibitors displayed remarkably higher inhibitory efficiency than their free counterparts. The research has shed new light on the design and fabrication of multifunctional nano-inhibitors.

Biography
Yan Sun completed his Bachelor of Chemical Engineering in Tianjin University in 1983. He then studied in the University of Tokyo from 1984, and received his Master and Doctor of Engineering Degrees in 1987 and 1990, respectively. After one-year working in a chemical company in Japan, he started his teaching and research career in Tianjin University and became a full Professor in 1993. In 2000, He earned the National Natural Science Foundation of China for Outstanding Young Scientists and was appointed to the Cheung Kong Professorship by the Ministry of Education of China. His areas of expertise include bioseparations, protein refolding, inhibition of amyloid protein aggregation, protein ligand design and discovery, and biocatalysis. His work has produced 360 research papers, a single book (Bioseparations Engineering), two book chapters and 40 patents. He is now an Editor of Journal of Chromatography A, Associate Editor of Biochemical Engineering Journal, and Associate Editor of Chinese Journal of Chemical Engineering.

Host: Professor Daniel Otzen, iNANO & Department of Molecular Biology and Genetics, Aarhus University

Coffe, tea and bread will be served from 10:00 in front of the auditorium.