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

ALMIRON ROMINA; CECILIA, TETTAMANTI; MARTINEZ SOFÍA M.; ANTONINO M; LORENZO A.; ALBERTO ALLEMANDI, DANIEL; DANIELA QUINTEROS; ANAHÍ E. BIGNANTE

Congreso; XXXVII Reunión Anual de la SAN; 2022

SAN

Alzheimer´s disease (AD) is a neurodegenerative pathology characterized by brain deposition of amyloid beta (Aβ). Gallein (GAL), a specific Gβγ inhibitor, greatly attenuates the exacerbated β-processing of APP and prevents intracellular accumulationof Aβ42 triggered by Aβ assemblies. The chronic administration of GAL appears as a promising therapy to treat AD, by avoiding the encounter between APP and BACE1 induced by Aβ. GAL is an experimental drug that has shown efficacy in preclinicalmodels 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 platformsfor 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, biodegradablepolymer that also acts as a key endogenous inhibitor of Aβ 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 vitrocharacterization of gallein-loaded nanoparticles of human albumin for further evaluation in vivo models of AD.