123rd General Meeting of the KCS

Type Poster Presentation
Area Life Chemistry
Room No. Exhibition Hall 2
Time 4월 19일 (금요일) 11:00~12:30
Code LIFE.P-340
Subject Characterizing Hetero-oligomer from Amyloid-beta and Alpha-synuclein with Bio-AFM
Authors Eun Ji Shin, Joon Won Park*
Department of Chemistry, Pohang University of Science and Technology, Korea
Abstract Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are neurodegenerative diseases resulting in progressive degeneration or death of neuron cells. These are associated with the aggregation of peptides, “Amyloid-beta (Aβ)” and “Alpha-synuclein (α-syn)”, respectively which are believed to be primarily responsible for the pathogenesis. Further study showed that there are a large number of patients with symptoms of both diseases at the same time and these patients are known to have a faster disease progression and worse prognosis than pure AD or PD patients. It is also known that the rate of the oligomerization (or aggregation) increases when Aβ and α-syn co-exist, and the co-existence causes the diseases to be even worse. It is very likely that hetero-oligomers could be formed, but the presence and structure of the hetero-oligomers have not been elucidated. Herein, we employed atomic force spectroscopy with a liquid cell to characterize the hetero-oligomers generated in vitro. For comparison, homo-oligomers were prepared separately. In particular, antibodies recognizing the N-terminal of Aβ and N-terminal of α-syn were conjugated at AFM probes, and the specific interaction between the antibodies and surface of the oligomers was observed1,2. After adsorbing the oligomers on a mica surface, a tip tethering Aβ antibody was used to get high resolution force maps of a target oligomer, and subsequently another tip tethering α-syn antibody was brought to the same target for the examination. The overlaid map revealed that specific unbinding events with respect to the two different antibodies were observed within an oligomer, and it holds true for all sizes under investigation. Because homo-oligomers were not observed at all, it can be said that formation of hetero-oligomers is strongly favored. It is intriguing to note that the percentage of recognized pixels for α-syn is higher than with the α-syn homo-oligomer, suggesting a different mode of aggregation for the hetero-oligomerization. We believe that such structural information will help to understand the relationship between the misfolded hetero-proteins and the pathogenesis in brain. References 1. Y. J. Jung, B. J. Hong, W. Zhang, S. J. Tendler, P. M. Williams, S. Allen, J. W. Park, J. Am. Chem. Soc. 129, 9349 (2007). 2. D. H. Kim, J.-E. Lee, Z.Y. Xu, K. R. Geem, Y. Kwon, J. W. Park, I. Hwang, Nat. Commun. 6, 6843 (2015). Acknowledgement This work is supported by the KGPF (Korea Global Ph.D. Fellows) from NRF (National Research Foundation of Korea).
E-mail shinej@postech.ac.kr