S-077 | Neuroprotective Effects of Gallein-Loaded Human Albumin Nanoparticles on a Human iPSC-Derived Neurons of model of Alzheimer’s disease

Disorders of the Nervous System
Author: ROMINA SOLEDAD ALMIRON | Email: ralmiron@immf.uncor.edu

Romina Soledad Almiron^1°, Cecilia Tettamanti^2°, Sofia Martinez^2°,  Magdalena Antonino^1°, Alfredo Lorenzo^1°, Daniel Allemandi^2°, Daniela Quinteros^2°,  Elena Anahi Bignante^1°

^1° INIMEC-UNC-CONICET
^2° UNITEFA-UNC

Previously, our group managed to synthesize human serum albumin (NP) nanoparticles, both pure and loaded with gallein (NP-GAL) through a desolvation and thermal stabilization technique. NPs were evaluated in in vitro models of Alzheimer’s disease (AD), using N2a cells and cortical neurons from rat embryos (RCN) treated with beta-amyloid (Aβ). The results validated the NP-GAL preparation method and demonstrated the effectiveness of these NPs in mitigating Aβ-induced toxicity in RCN. To explore the therapeutic potential of NP-GAL in the modulation of the Gβγ signaling pathway, key in the pathogenesis of AD, in a more complex and relevant in vitro model we used human neurons (HN) derived from induced pluripotent stem cells. We validated the model by demonstrating the toxic effect of Aβ on HNs, evidenced by marked neuritic dystrophy and decreased synaptophysin expression. We evaluated the protective effect of NPs and NP-GAL against Aβ-induced toxicity; we observed that NP-GAL significantly attenuated both neuritic dystrophy and synaptophysin loss induced by Aβ. This suggests that NP-GAL could exert a neuroprotective effect through modulation of the Gβγ signaling pathway, which represents a novel and promising mechanism of action for the treatment of AD. We also observed a protective effect of NPs; total on dystrophy and partial on Aβ-induced synaptic dysfunction. Our results support the therapeutic potential of GAL-NPs by modulating the Gβγ signaling pathway and of NPs per se.