GALLEIN-LOADED NANOPARTICLES OF HUMAN ALBUMIN ARE EFFECTIVE PREVENTING THE TOXIC EFFECTS OF ABETA IN VITRO MODELS OF ALZHEIMER?S DISEASE.

ALMIRON, ROMINA; ANTONINO, MAGDALENA; QUINTEROS, DA; MARTINEZ, S; ALLEMANDI, D; TETTAMANTI, C; LORENZO, ALFREDO; BIGNANTE, ELENA ANAHI

Tegucigalpa

Congreso; 2nd International Symposium LatBrain Initiative.; 2022

LatinBrain

Alzheimer´s disease (AD) is a neurodegenerative pathology characterized by brain deposition of amyloid beta (Abeta). Gallein (GAL), a specific Gbeta-gamma inhibitor, greatly attenuates the exacerbated beta-processing of APP and prevents intracellular accumulation of Abeta42 triggered by Abeta assemblies. The chronic administration of GAL appears as a promising therapy to treat AD, by avoiding the encounter between APP and BACE1 induced by Abeta. GAL is an experimental drug that has shown efficacy in preclinical models and no toxic effects have been reported in rodents. However, GAL has low water solubility and there is no information on its brain bioavailability. Protein-based biomaterials are being used in the synthesis of nanoparticles (NP) as platforms for the transport and release of drugs, being biodegradable and versatile. In this work we design and develop nanotechnological systems based on Human Serum Albumin (HSA) that allow the transport of GAL. ASH is a non-toxic, biodegradable polymer that also acts as a key endogenous inhibitor of Abeta aggregation. Inhibition of amyloid aggregation by HSA has therapeutic potential, but the underlying molecular mechanism remains elusive. The objective of this work is the design and in vitro characterization of gallein-loaded nanoparticles of human albumin for further evaluation in vivo models of AD.