Cargando…

α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study

Alzheimer’s disease (AD) is the most common form of dementia worldwide. The hallmarks of AD are the extracellular amyloid plaques, which are formed by amyloid β (Aβ) aggregates derived from the processing of the amyloid precursor protein (APP), and the intraneuronal neurofibrillary tangles, which ar...

Descripción completa

Detalles Bibliográficos
Autores principales: Gugliandolo, Agnese, Chiricosta, Luigi, Silvestro, Serena, Bramanti, Placido, Mazzon, Emanuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721308/
https://www.ncbi.nlm.nih.gov/pubmed/31405115
http://dx.doi.org/10.3390/brainsci9080196
_version_ 1783448315535294464
author Gugliandolo, Agnese
Chiricosta, Luigi
Silvestro, Serena
Bramanti, Placido
Mazzon, Emanuela
author_facet Gugliandolo, Agnese
Chiricosta, Luigi
Silvestro, Serena
Bramanti, Placido
Mazzon, Emanuela
author_sort Gugliandolo, Agnese
collection PubMed
description Alzheimer’s disease (AD) is the most common form of dementia worldwide. The hallmarks of AD are the extracellular amyloid plaques, which are formed by amyloid β (Aβ) aggregates derived from the processing of the amyloid precursor protein (APP), and the intraneuronal neurofibrillary tangles, which are formed by the hyperphosphorylated tau protein. The aim of this work was to study the effects of α-tocopherol in retinoic acid differentiated SH-SY5Y neuroblastoma cells exposed to Aβ(1-42) evaluating the transcriptional profile by next-generation sequencing. We observed that α-tocopherol was able to reduce the cytotoxicity induced by Aβ treatment, as demonstrated by Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Moreover, the transcriptomic analysis evidenced that α-tocopherol treatment upregulated genes involved in the non-amyloidogenic processing of APP, while it downregulated the amyloidogenic pathway. Moreover, α-tocopherol modulated the expression of the genes involved in autophagy and the cell cycle, which are both known to be altered in AD. The treatment with α-tocopherol was also able to reduce oxidative stress, restoring nuclear factor erythroid-derived 2-like 2 (Nrf2) and decreasing inducible nitric oxide synthase (iNOS) levels, as demonstrated by immunocytochemistry.
format Online
Article
Text
id pubmed-6721308
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-67213082019-09-10 α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study Gugliandolo, Agnese Chiricosta, Luigi Silvestro, Serena Bramanti, Placido Mazzon, Emanuela Brain Sci Article Alzheimer’s disease (AD) is the most common form of dementia worldwide. The hallmarks of AD are the extracellular amyloid plaques, which are formed by amyloid β (Aβ) aggregates derived from the processing of the amyloid precursor protein (APP), and the intraneuronal neurofibrillary tangles, which are formed by the hyperphosphorylated tau protein. The aim of this work was to study the effects of α-tocopherol in retinoic acid differentiated SH-SY5Y neuroblastoma cells exposed to Aβ(1-42) evaluating the transcriptional profile by next-generation sequencing. We observed that α-tocopherol was able to reduce the cytotoxicity induced by Aβ treatment, as demonstrated by Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Moreover, the transcriptomic analysis evidenced that α-tocopherol treatment upregulated genes involved in the non-amyloidogenic processing of APP, while it downregulated the amyloidogenic pathway. Moreover, α-tocopherol modulated the expression of the genes involved in autophagy and the cell cycle, which are both known to be altered in AD. The treatment with α-tocopherol was also able to reduce oxidative stress, restoring nuclear factor erythroid-derived 2-like 2 (Nrf2) and decreasing inducible nitric oxide synthase (iNOS) levels, as demonstrated by immunocytochemistry. MDPI 2019-08-10 /pmc/articles/PMC6721308/ /pubmed/31405115 http://dx.doi.org/10.3390/brainsci9080196 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gugliandolo, Agnese
Chiricosta, Luigi
Silvestro, Serena
Bramanti, Placido
Mazzon, Emanuela
α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_full α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_fullStr α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_full_unstemmed α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_short α-Tocopherol Modulates Non-Amyloidogenic Pathway and Autophagy in an In Vitro Model of Alzheimer’s Disease: A Transcriptional Study
title_sort α-tocopherol modulates non-amyloidogenic pathway and autophagy in an in vitro model of alzheimer’s disease: a transcriptional study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721308/
https://www.ncbi.nlm.nih.gov/pubmed/31405115
http://dx.doi.org/10.3390/brainsci9080196
work_keys_str_mv AT gugliandoloagnese atocopherolmodulatesnonamyloidogenicpathwayandautophagyinaninvitromodelofalzheimersdiseaseatranscriptionalstudy
AT chiricostaluigi atocopherolmodulatesnonamyloidogenicpathwayandautophagyinaninvitromodelofalzheimersdiseaseatranscriptionalstudy
AT silvestroserena atocopherolmodulatesnonamyloidogenicpathwayandautophagyinaninvitromodelofalzheimersdiseaseatranscriptionalstudy
AT bramantiplacido atocopherolmodulatesnonamyloidogenicpathwayandautophagyinaninvitromodelofalzheimersdiseaseatranscriptionalstudy
AT mazzonemanuela atocopherolmodulatesnonamyloidogenicpathwayandautophagyinaninvitromodelofalzheimersdiseaseatranscriptionalstudy