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Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study

The amyloid precursor protein (APP) processing pathway was altered in Alzheimer’s disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundament...

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Autores principales: Pahrudin Arrozi, Aslina, Shukri, Siti Nur Syazwani, Mohd Murshid, Nuraqila, Ahmad Shahzalli, Ahmad Baihaqi, Wan Ngah, Wan Zurinah, Ahmad Damanhuri, Hanafi, Makpol, Suzana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125555/
https://www.ncbi.nlm.nih.gov/pubmed/35614968
http://dx.doi.org/10.3389/fncel.2022.846459
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author Pahrudin Arrozi, Aslina
Shukri, Siti Nur Syazwani
Mohd Murshid, Nuraqila
Ahmad Shahzalli, Ahmad Baihaqi
Wan Ngah, Wan Zurinah
Ahmad Damanhuri, Hanafi
Makpol, Suzana
author_facet Pahrudin Arrozi, Aslina
Shukri, Siti Nur Syazwani
Mohd Murshid, Nuraqila
Ahmad Shahzalli, Ahmad Baihaqi
Wan Ngah, Wan Zurinah
Ahmad Damanhuri, Hanafi
Makpol, Suzana
author_sort Pahrudin Arrozi, Aslina
collection PubMed
description The amyloid precursor protein (APP) processing pathway was altered in Alzheimer’s disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundamental for AD modifying therapy. Extensive research has evaluated the protective effects of vitamin E as an antioxidant and as a signaling molecule. The present study aimed to investigate the modulatory effects of different tocopherol isomers on the expression of genes involved in regulating the APP processing pathway in vitro. The screening for the effective tocopherol isomers in reducing APP expression and Aβ-42 was carried out in SH-SY5Y stably overexpressed APP Swedish. Subsequently, quantitative one-step real-time PCR was performed to determine the modulatory effects of selected tocopherol isomers on the expression of genes in SH-SY5Y stably overexpressed three different types of APP (wild-type, APP Swedish, and APP Swedish/Indiana). Our results showed that all tocopherol isomers, especially at higher concentrations (80–100 μM), significantly increased (p < 0.05) the cell viability in all cells group, but only α-tocopherol (ATF) and γ-tocopherol (GTF) significantly decreased (p < 0.05) the APP mRNA level without statistically significant APP protein level, accompanied with a reduced significance (p < 0.05) on the level of Aβ-42 in SH-SY5Y APP Swedish. On the other hand, β- and δ-tocopherol (BTF and DTF) showed no effects on the level of APP expression and Aβ-42. Subsequent results demonstrated that ATF and GTF significantly decreased (p < 0.05) the expression of gene beta-site APP cleaving enzyme (BACE1), APH1B, and Nicastrin (NCSTN), but significantly increased (p < 0.05) the expression of Sirtuin 1 (SIRT1) in SH-SY5Y stably expressed the mutant APP form. These findings suggested that ATF and GTF could modulate altered pathways and may help ameliorate the burden of amyloid load in AD.
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spelling pubmed-91255552022-05-24 Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study Pahrudin Arrozi, Aslina Shukri, Siti Nur Syazwani Mohd Murshid, Nuraqila Ahmad Shahzalli, Ahmad Baihaqi Wan Ngah, Wan Zurinah Ahmad Damanhuri, Hanafi Makpol, Suzana Front Cell Neurosci Neuroscience The amyloid precursor protein (APP) processing pathway was altered in Alzheimer’s disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundamental for AD modifying therapy. Extensive research has evaluated the protective effects of vitamin E as an antioxidant and as a signaling molecule. The present study aimed to investigate the modulatory effects of different tocopherol isomers on the expression of genes involved in regulating the APP processing pathway in vitro. The screening for the effective tocopherol isomers in reducing APP expression and Aβ-42 was carried out in SH-SY5Y stably overexpressed APP Swedish. Subsequently, quantitative one-step real-time PCR was performed to determine the modulatory effects of selected tocopherol isomers on the expression of genes in SH-SY5Y stably overexpressed three different types of APP (wild-type, APP Swedish, and APP Swedish/Indiana). Our results showed that all tocopherol isomers, especially at higher concentrations (80–100 μM), significantly increased (p < 0.05) the cell viability in all cells group, but only α-tocopherol (ATF) and γ-tocopherol (GTF) significantly decreased (p < 0.05) the APP mRNA level without statistically significant APP protein level, accompanied with a reduced significance (p < 0.05) on the level of Aβ-42 in SH-SY5Y APP Swedish. On the other hand, β- and δ-tocopherol (BTF and DTF) showed no effects on the level of APP expression and Aβ-42. Subsequent results demonstrated that ATF and GTF significantly decreased (p < 0.05) the expression of gene beta-site APP cleaving enzyme (BACE1), APH1B, and Nicastrin (NCSTN), but significantly increased (p < 0.05) the expression of Sirtuin 1 (SIRT1) in SH-SY5Y stably expressed the mutant APP form. These findings suggested that ATF and GTF could modulate altered pathways and may help ameliorate the burden of amyloid load in AD. Frontiers Media S.A. 2022-05-05 /pmc/articles/PMC9125555/ /pubmed/35614968 http://dx.doi.org/10.3389/fncel.2022.846459 Text en Copyright © 2022 Pahrudin Arrozi, Shukri, Mohd Murshid, Ahmad Shahzalli, Wan Ngah, Ahmad Damanhuri and Makpol. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Pahrudin Arrozi, Aslina
Shukri, Siti Nur Syazwani
Mohd Murshid, Nuraqila
Ahmad Shahzalli, Ahmad Baihaqi
Wan Ngah, Wan Zurinah
Ahmad Damanhuri, Hanafi
Makpol, Suzana
Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_full Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_fullStr Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_full_unstemmed Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_short Alpha- and Gamma-Tocopherol Modulates the Amyloidogenic Pathway of Amyloid Precursor Protein in an in vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_sort alpha- and gamma-tocopherol modulates the amyloidogenic pathway of amyloid precursor protein in an in vitro model of alzheimer’s disease: a transcriptional study
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125555/
https://www.ncbi.nlm.nih.gov/pubmed/35614968
http://dx.doi.org/10.3389/fncel.2022.846459
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