Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis

Abstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder with impaired protein activities. Proteins in the form of complexes have a ubiquitous role in diverse range of cellular functions. The key challenge is to identify novel disease associated protein complexes and their potential...

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Autores principales:	Beena Hasan, Ayesha Khan, Christof Lenz, Abdul R. Asif, Nikhat Ahmed
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81369126a1bc48a28f685365a727eec7
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spelling	oai:doaj.org-article:81369126a1bc48a28f685365a727eec72021-12-02T18:34:20ZCharacterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis10.1038/s41598-021-93356-92045-2322https://doaj.org/article/81369126a1bc48a28f685365a727eec72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93356-9https://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder with impaired protein activities. Proteins in the form of complexes have a ubiquitous role in diverse range of cellular functions. The key challenge is to identify novel disease associated protein complexes and their potential role in the progression of AD pathology. Protein complexes were obtained from AD brain prefrontal cortex and age matched controls by Blue Native-Polyacrylamide Gel Electrophoresis. A proteomic analysis was performed using second dimension SDS-PAGE followed by nano LC–MS/MS. Differentially expressed proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). A total of 13 protein complexes with their interacting proteins were resolved on SDS-PAGE. We identified 34 protein spots and found significant abundance difference between the two experimental samples. IPA analysis revealed degeneration of neurons and cell death as a major consequence of protein dysregulation. Furthermore, focused network analysis suggested an integrated regulation of the identified proteins through APP and MAPT dependent mechanisms. The interacting differentially expressed proteins in AD were found to be part of concomitant signaling cascades terminating in neuronal cell death. The identified protein networks and pathways warrant further research to study their actual contribution to AD pathology.Beena HasanAyesha KhanChristof LenzAbdul R. AsifNikhat AhmedNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beena Hasan Ayesha Khan Christof Lenz Abdul R. Asif Nikhat Ahmed Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
description	Abstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder with impaired protein activities. Proteins in the form of complexes have a ubiquitous role in diverse range of cellular functions. The key challenge is to identify novel disease associated protein complexes and their potential role in the progression of AD pathology. Protein complexes were obtained from AD brain prefrontal cortex and age matched controls by Blue Native-Polyacrylamide Gel Electrophoresis. A proteomic analysis was performed using second dimension SDS-PAGE followed by nano LC–MS/MS. Differentially expressed proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). A total of 13 protein complexes with their interacting proteins were resolved on SDS-PAGE. We identified 34 protein spots and found significant abundance difference between the two experimental samples. IPA analysis revealed degeneration of neurons and cell death as a major consequence of protein dysregulation. Furthermore, focused network analysis suggested an integrated regulation of the identified proteins through APP and MAPT dependent mechanisms. The interacting differentially expressed proteins in AD were found to be part of concomitant signaling cascades terminating in neuronal cell death. The identified protein networks and pathways warrant further research to study their actual contribution to AD pathology.
format	article
author	Beena Hasan Ayesha Khan Christof Lenz Abdul R. Asif Nikhat Ahmed
author_facet	Beena Hasan Ayesha Khan Christof Lenz Abdul R. Asif Nikhat Ahmed
author_sort	Beena Hasan
title	Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
title_short	Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
title_full	Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
title_fullStr	Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
title_full_unstemmed	Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
title_sort	characterization of functional protein complexes from alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/81369126a1bc48a28f685365a727eec7
work_keys_str_mv	AT beenahasan characterizationoffunctionalproteincomplexesfromalzheimersdiseaseandhealthybrainbymassspectrometrybasedproteomeanalysis AT ayeshakhan characterizationoffunctionalproteincomplexesfromalzheimersdiseaseandhealthybrainbymassspectrometrybasedproteomeanalysis AT christoflenz characterizationoffunctionalproteincomplexesfromalzheimersdiseaseandhealthybrainbymassspectrometrybasedproteomeanalysis AT abdulrasif characterizationoffunctionalproteincomplexesfromalzheimersdiseaseandhealthybrainbymassspectrometrybasedproteomeanalysis AT nikhatahmed characterizationoffunctionalproteincomplexesfromalzheimersdiseaseandhealthybrainbymassspectrometrybasedproteomeanalysis
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Characterization of functional protein complexes from Alzheimer’s disease and healthy brain by mass spectrometry-based proteome analysis

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