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The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers

In Alzheimer’s disease (AD), accumulation of amyloid β-protein (Aβ) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by Aβ has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce Aβ-induced toxici...

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Autores principales: Momma, Yutaro, Tsuji, Mayumi, Oguchi, Tatsunori, Ohashi, Hideaki, Nohara, Tetsuhito, Ito, Naohito, Yamamoto, Ken, Nagata, Miki, Kimura, Atsushi Michael, Nakamura, Shiro, Kiuchi, Yuji, Ono, Kenjiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960433/
https://www.ncbi.nlm.nih.gov/pubmed/36834498
http://dx.doi.org/10.3390/ijms24043089
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author Momma, Yutaro
Tsuji, Mayumi
Oguchi, Tatsunori
Ohashi, Hideaki
Nohara, Tetsuhito
Ito, Naohito
Yamamoto, Ken
Nagata, Miki
Kimura, Atsushi Michael
Nakamura, Shiro
Kiuchi, Yuji
Ono, Kenjiro
author_facet Momma, Yutaro
Tsuji, Mayumi
Oguchi, Tatsunori
Ohashi, Hideaki
Nohara, Tetsuhito
Ito, Naohito
Yamamoto, Ken
Nagata, Miki
Kimura, Atsushi Michael
Nakamura, Shiro
Kiuchi, Yuji
Ono, Kenjiro
author_sort Momma, Yutaro
collection PubMed
description In Alzheimer’s disease (AD), accumulation of amyloid β-protein (Aβ) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by Aβ has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce Aβ-induced toxicity; however, due to its low bioavailability, clinical trials showed no remarkable effect on cognitive function. As a result, GT863, a derivative of curcumin with higher bioavailability, was synthesized. The purpose of this study is to clarify the mechanism of the protective action of GT863 against the neurotoxicity of highly toxic Aβ oligomers (Aβo), which include high-molecular-weight (HMW) Aβo, mainly composed of protofibrils in human neuroblastoma SH-SY5Y cells, focusing on the cell membrane. The effect of GT863 (1 μM) on Aβo-induced membrane damage was assessed by phospholipid peroxidation of the membrane, membrane fluidity, membrane phase state, membrane potential, membrane resistance, and changes in intracellular Ca(2+) ([Ca(2+)]i). GT863 inhibited the Aβo-induced increase in plasma-membrane phospholipid peroxidation, decreased membrane fluidity and resistance, and decreased excessive [Ca(2+)]i influx, showing cytoprotective effects. The effects of GT863 on cell membranes may contribute in part to its neuroprotective effects against Aβo-induced toxicity. GT863 may be developed as a prophylactic agent for AD by targeting inhibition of membrane disruption caused by Aβo exposure.
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spelling pubmed-99604332023-02-26 The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers Momma, Yutaro Tsuji, Mayumi Oguchi, Tatsunori Ohashi, Hideaki Nohara, Tetsuhito Ito, Naohito Yamamoto, Ken Nagata, Miki Kimura, Atsushi Michael Nakamura, Shiro Kiuchi, Yuji Ono, Kenjiro Int J Mol Sci Article In Alzheimer’s disease (AD), accumulation of amyloid β-protein (Aβ) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by Aβ has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce Aβ-induced toxicity; however, due to its low bioavailability, clinical trials showed no remarkable effect on cognitive function. As a result, GT863, a derivative of curcumin with higher bioavailability, was synthesized. The purpose of this study is to clarify the mechanism of the protective action of GT863 against the neurotoxicity of highly toxic Aβ oligomers (Aβo), which include high-molecular-weight (HMW) Aβo, mainly composed of protofibrils in human neuroblastoma SH-SY5Y cells, focusing on the cell membrane. The effect of GT863 (1 μM) on Aβo-induced membrane damage was assessed by phospholipid peroxidation of the membrane, membrane fluidity, membrane phase state, membrane potential, membrane resistance, and changes in intracellular Ca(2+) ([Ca(2+)]i). GT863 inhibited the Aβo-induced increase in plasma-membrane phospholipid peroxidation, decreased membrane fluidity and resistance, and decreased excessive [Ca(2+)]i influx, showing cytoprotective effects. The effects of GT863 on cell membranes may contribute in part to its neuroprotective effects against Aβo-induced toxicity. GT863 may be developed as a prophylactic agent for AD by targeting inhibition of membrane disruption caused by Aβo exposure. MDPI 2023-02-04 /pmc/articles/PMC9960433/ /pubmed/36834498 http://dx.doi.org/10.3390/ijms24043089 Text en © 2023 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
Momma, Yutaro
Tsuji, Mayumi
Oguchi, Tatsunori
Ohashi, Hideaki
Nohara, Tetsuhito
Ito, Naohito
Yamamoto, Ken
Nagata, Miki
Kimura, Atsushi Michael
Nakamura, Shiro
Kiuchi, Yuji
Ono, Kenjiro
The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title_full The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title_fullStr The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title_full_unstemmed The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title_short The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers
title_sort curcumin derivative gt863 protects cell membranes in cytotoxicity by aβ oligomers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960433/
https://www.ncbi.nlm.nih.gov/pubmed/36834498
http://dx.doi.org/10.3390/ijms24043089
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