Protective Role of a Donepezil-Huprine Hybrid against the beta-Amyloid (1-42) Effect on Human Erythrocytes

Zambrano, Pablo; Suwalsky, Mario; Jemiola-Rzeminska, Malgorzata; Jose Gallardo-Nelson, Maria; Strzalka, Kazimierz; Munoz-Torrero, Diego

Abstract

A beta(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer's disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent A beta(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express A beta(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by A beta(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by A beta(1-42) peptide in human erythrocytes and molecular models.

Más información

Título según WOS: ID WOS:000694331700001 Not found in local WOS DB
Título de la Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volumen: 22
Número: 17
Editorial: MDPI
Fecha de publicación: 2021
DOI:

10.3390/ijms22179563

Notas: ISI