Using Amyloid β42 Mutant F19S L34P as Amyloid β42 Aggregation Inhibitor

Ofek Oren ofekor@post.bgu.ac.il ^1,2 Ran Taube ¹ Niv Papo ²

¹Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
²Department of Biotechnology Engineering and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Amyloids are insoluble misfolded proteins that often aggregate into typical fibrils forms, which are rich with β-sheet elements and are associated with the pathology of human neurodegenerative diseases. During the last decade, great efforts have been put into identifying new inhibitors that target amyloid aggregation. However, the understanding of the molecular mechanisms that induce amyloid-mediated neuronal cell death is limited, and the search for efficient treatments is still ongoing. Therefore, developing novel amyloid aggregation inhibitors is of high interest.

With roughly 44 million worldwide diagnostic patients, Alzheimer`s disease is the most common neurodegenerative disease, and Amyloid β42 (Aβ42) is the amyloid most associated with the disease pathology.

In this study, we chose to employ and characterized Aβ42 mutant, F19S L34P (Aβ42_DM), a non-aggregating mutant, as an inhibitor for Aβ42 aggregation, using mammalian cells platform to investigate its activity.

As our preliminary results show, Aβ42_DM decreases Aβ42 aggregation in mammalian cells and reducing Aβ42 toxic effect.

In our search for novel functional inhibitors that target amyloid aggregation, this work exhibits unique features of experimental methodologies performed in human cells to accelerate the identification of efficient inhibitors against Aβ42 aggregation in our efforts to treat neurodegenerative diseases.