Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients

Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies includ...

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Main Authors: Callum N. Watson, Ghazala Begum, Emma Ashman, Daniella Thorn, Kamal M. Yakoub, Moustafa Al Hariri, Ali Nehme, Stefania Mondello, Firas Kobeissy, Antonio Belli, Valentina Di Pietro
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/1/163
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author Callum N. Watson
Ghazala Begum
Emma Ashman
Daniella Thorn
Kamal M. Yakoub
Moustafa Al Hariri
Ali Nehme
Stefania Mondello
Firas Kobeissy
Antonio Belli
Valentina Di Pietro
author_facet Callum N. Watson
Ghazala Begum
Emma Ashman
Daniella Thorn
Kamal M. Yakoub
Moustafa Al Hariri
Ali Nehme
Stefania Mondello
Firas Kobeissy
Antonio Belli
Valentina Di Pietro
author_sort Callum N. Watson
collection DOAJ
description Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.
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spelling doaj.art-ac1351a014ed437a96f031422989f4822023-11-23T11:21:08ZengMDPI AGCells2073-44092022-01-0111116310.3390/cells11010163Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease PatientsCallum N. Watson0Ghazala Begum1Emma Ashman2Daniella Thorn3Kamal M. Yakoub4Moustafa Al Hariri5Ali Nehme6Stefania Mondello7Firas Kobeissy8Antonio Belli9Valentina Di Pietro10Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKDepartment of Emergency Medicine, American University of Beirut Medical Center, Beirut 1107 2020, LebanonInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98165 Messina, ItalyProgram for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USAInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKAlzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.https://www.mdpi.com/2073-4409/11/1/163Alzheimer’s diseasemicroRNA profileprotein profileco-expression analysisRap1 signalling
spellingShingle Callum N. Watson
Ghazala Begum
Emma Ashman
Daniella Thorn
Kamal M. Yakoub
Moustafa Al Hariri
Ali Nehme
Stefania Mondello
Firas Kobeissy
Antonio Belli
Valentina Di Pietro
Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
Cells
Alzheimer’s disease
microRNA profile
protein profile
co-expression analysis
Rap1 signalling
title Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
title_full Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
title_fullStr Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
title_full_unstemmed Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
title_short Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients
title_sort co expression analysis of micrornas and proteins in brain of alzheimer s disease patients
topic Alzheimer’s disease
microRNA profile
protein profile
co-expression analysis
Rap1 signalling
url https://www.mdpi.com/2073-4409/11/1/163
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