Identification of β‐aminopyrrolidine containing peptides as β‐amyloid aggregation inhibitors for Alzheimer's disease

Alzheimer's disease (AD) is caused by a series of events initiated by the production and aggregation of the amyloid β‐protein (Aβ). In the early stages of the disease, Aβ is released in a soluble form then progressively forms oligomeric, multimeric, and fibrillar aggregates, triggering neurodegeneration. Thus, development of inhibitors that initiate reverse Aβ aggregation is thought to be a logical approach in treating AD. In this context, we developed β‐aminopyrrolidine containing 12 mer peptide 3 which is very potent in inhibiting the Aβ aggregation and also reducing Aβ(42)‐induced cytotoxicity. Soluble oligomers play a major role in neurodegenration. We have reported β‐aminopyrrolidine based Peptides 1 and 3, and they found to be effective not only in inhibiting Aβ(42) aggregation but also reduces Aβ(42) induced toxicity both in vitro and in vivo. Both peptides significantly reduced the formation of HMW oligomers and reduced their cytotoxicity.