A Snake Venom Peptide and Its Derivatives Prevent Aβ₄₂ Aggregation and Eliminate Toxic Aβ₄₂ Aggregates In Vitro

Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-β (Aβ) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system. In this study, nine peptide derivatives of Crotamine, a polypeptide from Crotalus durissus terrificus Rattlesnake venom, as well as one d-enantiomer, were evaluated for their ability to modulate Aβ₄₂ aggregation through various assays such as ThT, QIAD, SPR, and sFIDA. All tested peptides were able to decrease Aβ₄₂ aggregation and eliminate Aβ₄₂ aggregates. Additionally, all of the peptides showed an affinity for Aβ₄₂. This study is the first to describe the potential of crotamine derivative peptides against Aβ₄₂ aggregation and to identify a promising d-peptide that could be used as an effective pharmacological tool against AD in the future.