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Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease

Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem c...

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Autores principales: Cavalli, Eugenio, Battaglia, Giuseppe, Basile, Maria Sofia, Bruno, Valeria, Petralia, Maria Cristina, Lombardo, Salvo Danilo, Pennisi, Manuela, Kalfin, Reni, Tancheva, Lyubka, Fagone, Paolo, Nicoletti, Ferdinando, Mangano, Katia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139610/
https://www.ncbi.nlm.nih.gov/pubmed/32183090
http://dx.doi.org/10.3390/brainsci10030166
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author Cavalli, Eugenio
Battaglia, Giuseppe
Basile, Maria Sofia
Bruno, Valeria
Petralia, Maria Cristina
Lombardo, Salvo Danilo
Pennisi, Manuela
Kalfin, Reni
Tancheva, Lyubka
Fagone, Paolo
Nicoletti, Ferdinando
Mangano, Katia
author_facet Cavalli, Eugenio
Battaglia, Giuseppe
Basile, Maria Sofia
Bruno, Valeria
Petralia, Maria Cristina
Lombardo, Salvo Danilo
Pennisi, Manuela
Kalfin, Reni
Tancheva, Lyubka
Fagone, Paolo
Nicoletti, Ferdinando
Mangano, Katia
author_sort Cavalli, Eugenio
collection PubMed
description Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from AD patients have proven to be a reliable model for AD pathogenesis. Here, we have conducted an in silico analysis aimed at identifying pathogenic gene-expression profiles and novel drug candidates. The GSE117589 microarray dataset was used for the identification of Differentially Expressed Genes (DEGs) between iPSC-derived neuronal progenitor (NP) cells and neurons from AD patients and healthy donors. The Discriminant Analysis Module (DAM) algorithm was used for the identification of biomarkers of disease. Drugs with anti-signature gene perturbation profiles were identified using the L1000FWD software. DAM analysis was used to identify a list of potential biomarkers among the DEGs, able to discriminate AD patients from healthy people. Finally, anti-signature perturbation analysis identified potential anti-AD drugs. This study set the basis for the investigation of potential novel pharmacological strategies for AD. Furthermore, a subset of genes for the early diagnosis of AD is proposed.
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spelling pubmed-71396102020-04-10 Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease Cavalli, Eugenio Battaglia, Giuseppe Basile, Maria Sofia Bruno, Valeria Petralia, Maria Cristina Lombardo, Salvo Danilo Pennisi, Manuela Kalfin, Reni Tancheva, Lyubka Fagone, Paolo Nicoletti, Ferdinando Mangano, Katia Brain Sci Article Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from AD patients have proven to be a reliable model for AD pathogenesis. Here, we have conducted an in silico analysis aimed at identifying pathogenic gene-expression profiles and novel drug candidates. The GSE117589 microarray dataset was used for the identification of Differentially Expressed Genes (DEGs) between iPSC-derived neuronal progenitor (NP) cells and neurons from AD patients and healthy donors. The Discriminant Analysis Module (DAM) algorithm was used for the identification of biomarkers of disease. Drugs with anti-signature gene perturbation profiles were identified using the L1000FWD software. DAM analysis was used to identify a list of potential biomarkers among the DEGs, able to discriminate AD patients from healthy people. Finally, anti-signature perturbation analysis identified potential anti-AD drugs. This study set the basis for the investigation of potential novel pharmacological strategies for AD. Furthermore, a subset of genes for the early diagnosis of AD is proposed. MDPI 2020-03-13 /pmc/articles/PMC7139610/ /pubmed/32183090 http://dx.doi.org/10.3390/brainsci10030166 Text en © 2020 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
Cavalli, Eugenio
Battaglia, Giuseppe
Basile, Maria Sofia
Bruno, Valeria
Petralia, Maria Cristina
Lombardo, Salvo Danilo
Pennisi, Manuela
Kalfin, Reni
Tancheva, Lyubka
Fagone, Paolo
Nicoletti, Ferdinando
Mangano, Katia
Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title_full Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title_fullStr Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title_full_unstemmed Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title_short Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
title_sort exploratory analysis of ipscs-derived neuronal cells as predictors of diagnosis and treatment of alzheimer disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139610/
https://www.ncbi.nlm.nih.gov/pubmed/32183090
http://dx.doi.org/10.3390/brainsci10030166
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