Evaluation of Antiamyloidogenic Peptides for the Treatment of Alzheimer's Disease and Their Effects on the Blood-Brain Barrier
Alzheimer’s Disease, Peptide, Neuropharmacology, Blood-brainbarrier
Alzheimer's disease (AD) is the leading cause of dementia worldwide, and currently available treatments act predominantly on symptoms, without modifying the underlying pathological processes. In this context, peptides bioinspired by wasp venoms emerge as a promising therapeutic alternative, due to their high selectivity and low toxicity. This study aims to evaluate the therapeutic potential of two antiamyloidogenic peptides, Alzpeptidina and GLP1-f, as well as to investigate a novel brain delivery strategy for Octovespina, a peptide previously characterized by the research group. In vitro assays were performed to assess amyloid-beta (Aβ) aggregation by thioflavin T, cytotoxicity by MTT, hemolytic potential, oxidative stress induction, and blood-brain barrier (BBB) permeability in a human co-culture model, in addition to stability and acute toxicity tests in a murine model. The results showed that Alzpeptidina (100 µM) and GLP1-f (10 µM) exhibited significant antiaggregant effects on Aβ, with distinct kinetic profiles, without inducing cytotoxicity, hemolysis, or oxidative stress at any of the concentrations tested. GLP1-f was able to cross the in vitro BBB model, whereas Alzpeptidina was not detected in the receiver compartment, suggesting a possible interaction with the membrane of the system used. Both peptides remained stable under refrigeration for up to 30 days, while GLP1-f degraded at room temperature. Preliminary in vivo acute toxicity results, assessed thus far for GLP1-f, showed no relevant changes in body mass or relative organ mass. Together, these findings reinforce the therapeutic potential of Alzpeptidina and GLP1-f for the treatment of AD, while the ongoing investigation of Octovespina, combined with magnetic resonance-guided focused ultrasound, may help overcome the brain bioavailability limitations observed with its systemic administration.