The amyloid-inhibiting NCAM-PrP peptide targets Aβ peptide aggregation in membrane-mimetic environments

iScience

Mazin Magzoub¹  Astrid Gräslund²  Sylwia Król²  Jüri Jarvet²  Nicklas Österlund²  Faraz Vosough²  Sebastian Wärmländer²  Cecilia Mörman²  Andreas Barth²  Leopold L. Ilag³ 

[1] Biology Program, Division of Science, New York University Abu Dhabi, Box 129188, Abu Dhabi, United Arab Emirates;Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 106 91, Sweden;Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, 106 91, Sweden;

关键词: molecular neuroscience;    structural biology;    biophysics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Substantial research efforts have gone into elucidating the role of protein misfolding and self-assembly in the onset and progression of Alzheimer’s disease (AD). Aggregation of the Amyloid-β (Aβ) peptide into insoluble fibrils is closely associated with AD. Here, we use biophysical techniques to study a peptide-based approach to target Aβ amyloid aggregation. A peptide construct, NCAM-PrP, consists of a largely hydrophobic signal sequence linked to a positively charged hexapeptide. The NCAM-PrP peptide inhibits Aβ amyloid formation by forming aggregates which are unavailable for further amyloid aggregation. In a membrane-mimetic environment, Aβ and NCAM-PrP form specific heterooligomeric complexes, which are of lower aggregation states compared to Aβ homooligomers. The Aβ:NCAM-PrP interaction appears to take place on different aggregation states depending on the absence or presence of a membrane-mimicking environment. These insights can be useful for the development of potential future therapeutic strategies targeting Aβ at several aggregation states.

【 授权许可】

Unknown