Control of Morphology and Subsequent Toxicity of A¥â Amyloid Fibrils through the Dequalinium-induced Seed Modification

Bulletin of the Korean chemical society

Jina Kim¹  Seung R. Paik¹  Eun-Kyung Myung¹  In-Hwan Lee¹ 

关键词: A¥â;    Dequalinium;    Seeding effect;    Amyloid fibrils;    Alzheimer¡¯s disease;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Amyloid fibril formation of amyloid �?/A4 protein (A�?) is critical to understand the pathological mechanism of Alzheimer’s disease and develop controlling strategy toward the neurodegenerative disease. For this purpose, dequalinium (DQ) has been employed as a specific modifier for A�? aggregation and its subsequent cytotoxicity. In the presence of DQ, the final thioflavin-T binding fluorescence of A�? aggregates decreased significantly. It was the altered morphology of A�? aggregates in a form of the bundles of the fibrils, distinctive from normal single-stranded amyloid fibrils, and the resulting reduced �?-sheet content that were responsible for the decreased fluorescence. The morphological transition of A�? aggregates assessed with atomic force microscope indicated that the bundle structure observed with DQ appeared to be resulted from the initial multimeric seed structure rather than lateral association of preformed single-stranded fibrils. Investigation of the seeding effect of the DQ-induced A�? aggregates clearly demonstrated that the seed structure has determined the final morphology of A�? aggregates as well as the aggregative kinetics by shortening the lag phase. In addition, the cytotoxicity was also varied depending on the final morphology of the aggregates. Taken together, DQ has been considered to be a useful chemical probe to control the cytotoxicity of the amyloid fibrils by influencing the seed structures which turned out to be central to develop therapeutic strategy by inducing the amyloid fibrils in different shapes with varied toxicities.

【 授权许可】

Unknown