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Article

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

1
Facultad de Ciencias Químicas, Universidad de Concepción, Concepción 4030000, Chile
2
Facultad de Medicina, Universidad Católica de la Santísima Concepción, Concepción 4030000, Chile
3
Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland
4
Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland
5
School of Medicine, University of Atacama, Copiapó 1530000, Chile
6
Laboratory of Medicinal Chemistry (CSIC Associated Unit), Faculty of Pharmacy and Food, Sciences, University of Barcelona (UB), E-08028 Barcelona, Spain
7
Institute of Biomedicine (IBUB), University of Barcelona (UB), E-08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Current address: Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Academic Editor: Maria Laura Giuffrida
Int. J. Mol. Sci. 2021, 22(17), 9563; https://doi.org/10.3390/ijms22179563
Received: 4 August 2021 / Revised: 27 August 2021 / Accepted: 31 August 2021 / Published: 3 September 2021
Aβ(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 Aβ(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 Aβ(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 Aβ(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 Aβ(1-42) peptide in human erythrocytes and molecular models. View Full-Text
Keywords: AVCRI104P4; beta-amyloid; cell membrane; lipid bilayer; human erythrocyte; acetylcholinesterase; multitarget agent AVCRI104P4; beta-amyloid; cell membrane; lipid bilayer; human erythrocyte; acetylcholinesterase; multitarget agent
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MDPI and ACS Style

Zambrano, P.; Suwalsky, M.; Jemiola-Rzeminska, M.; Gallardo-Nelson, M.J.; Strzalka, K.; Muñoz-Torrero, D. Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes. Int. J. Mol. Sci. 2021, 22, 9563. https://doi.org/10.3390/ijms22179563

AMA Style

Zambrano P, Suwalsky M, Jemiola-Rzeminska M, Gallardo-Nelson MJ, Strzalka K, Muñoz-Torrero D. Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes. International Journal of Molecular Sciences. 2021; 22(17):9563. https://doi.org/10.3390/ijms22179563

Chicago/Turabian Style

Zambrano, Pablo, Mario Suwalsky, Malgorzata Jemiola-Rzeminska, María J. Gallardo-Nelson, Kazimierz Strzalka, and Diego Muñoz-Torrero. 2021. "Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes" International Journal of Molecular Sciences 22, no. 17: 9563. https://doi.org/10.3390/ijms22179563

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