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A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells

Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the a...

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Autores principales: Mladenova, Kirilka, Stavrakov, Georgi, Philipova, Irena, Atanasova, Mariyana, Petrova, Svetla, Doumanov, Jordan, Doytchinova, Irini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307467/
https://www.ncbi.nlm.nih.gov/pubmed/34299209
http://dx.doi.org/10.3390/ijms22147592
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author Mladenova, Kirilka
Stavrakov, Georgi
Philipova, Irena
Atanasova, Mariyana
Petrova, Svetla
Doumanov, Jordan
Doytchinova, Irini
author_facet Mladenova, Kirilka
Stavrakov, Georgi
Philipova, Irena
Atanasova, Mariyana
Petrova, Svetla
Doumanov, Jordan
Doytchinova, Irini
author_sort Mladenova, Kirilka
collection PubMed
description Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the ability to stimulate allosterically the α7 nAChRs and to regulate the calcium cytosolic concentration. Here, we examined the cytoprotective effects of two GAL derivatives, namely compounds 4b and 8, against Aβ cytotoxicity on the human neuroblastoma cell line SH-SY5Y. The protective effects were tested at simultaneous administration, pre-incubation and post-incubation, with Aβ. GAL and curcumin (CU) were used in the study as reference compounds. It was found that 4b protects cells in a similar mode as GAL, while compound 8 and CU potentiate the toxic effects of Aβ. Allosteric stimulation of α7 nAChRs is suggested as a possible mechanism of the cytoprotectivity of 4b. These and previous findings characterize 4b as a prospective non-toxic multi-target agent against neurodegenerative disorders with inhibitory activity on acetylcholinesterase, antioxidant, and cytoprotective properties.
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spelling pubmed-83074672021-07-25 A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells Mladenova, Kirilka Stavrakov, Georgi Philipova, Irena Atanasova, Mariyana Petrova, Svetla Doumanov, Jordan Doytchinova, Irini Int J Mol Sci Article Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the ability to stimulate allosterically the α7 nAChRs and to regulate the calcium cytosolic concentration. Here, we examined the cytoprotective effects of two GAL derivatives, namely compounds 4b and 8, against Aβ cytotoxicity on the human neuroblastoma cell line SH-SY5Y. The protective effects were tested at simultaneous administration, pre-incubation and post-incubation, with Aβ. GAL and curcumin (CU) were used in the study as reference compounds. It was found that 4b protects cells in a similar mode as GAL, while compound 8 and CU potentiate the toxic effects of Aβ. Allosteric stimulation of α7 nAChRs is suggested as a possible mechanism of the cytoprotectivity of 4b. These and previous findings characterize 4b as a prospective non-toxic multi-target agent against neurodegenerative disorders with inhibitory activity on acetylcholinesterase, antioxidant, and cytoprotective properties. MDPI 2021-07-15 /pmc/articles/PMC8307467/ /pubmed/34299209 http://dx.doi.org/10.3390/ijms22147592 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mladenova, Kirilka
Stavrakov, Georgi
Philipova, Irena
Atanasova, Mariyana
Petrova, Svetla
Doumanov, Jordan
Doytchinova, Irini
A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title_full A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title_fullStr A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title_full_unstemmed A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title_short A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells
title_sort galantamine–curcumin hybrid decreases the cytotoxicity of amyloid-beta peptide on sh-sy5y cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307467/
https://www.ncbi.nlm.nih.gov/pubmed/34299209
http://dx.doi.org/10.3390/ijms22147592
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