Combating amyloid-induced cellular toxicity and stiffness by designer peptidomimetics

Amyloid beta (Aβ) aggregation species-associated cellular stress instigates cytotoxicity and adverse cellular stiffness in neuronal cells. The study and modulation of these adverse effects demand immediate attention to tackle Alzheimer's disease (AD). We present a de novo design, synthesis and evaluation of Aβ14-23 peptidomimetics with cyclic dipeptide (CDP) units at defined positions. Our study identified Akd^NMC with CDP units at the middle, N- and C-termini as a potent candidate to understand and ameliorate Aβ aggregation-induced cellular toxicity and adverse stiffness.