Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes

The chronic irreversible regression of cognitive ability and memory function in human immunodeficiency virus (HIV)-associated dementia (HAND) is linked with late-stage HIV infection in the brain. The molecular-level signatures of neuroinflammation and neurodegeneration are linked with dysfunction in...

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Autores principales: Mayur Doke, Tamizhselvi Ramasamy, Vaishnavi Sundar, Jay P. McLaughlin, Thangavel Samikkannu
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0ff0bf98961a4dcea3b62196442b2f072021-11-25T16:57:24ZProteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes10.3390/brainsci111114382076-3425https://doaj.org/article/0ff0bf98961a4dcea3b62196442b2f072021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1438https://doaj.org/toc/2076-3425The chronic irreversible regression of cognitive ability and memory function in human immunodeficiency virus (HIV)-associated dementia (HAND) is linked with late-stage HIV infection in the brain. The molecular-level signatures of neuroinflammation and neurodegeneration are linked with dysfunction in HAND patients. Protein expression changes and posttranslational modification are epigenetic cues for dementia and neurodegenerative disease. In this study quantitative proteome analysis was performed to comprehensively elucidate changes in protein profiles in HIV-positive (HIV+) human brains. Frontal and temporal lobes of normal and HIV+ brains were subjected to label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using the data-independent acquisition method. Comprehensive proteomic identification and quantification analysis revealed that 3294 total proteins and 251 proteins were differentially expressed in HIV+ brains; specifically, HIV+ frontal and temporal lobes had 132 and 119 differentially expressed proteins, respectively. Proteomic and bioinformatic analyses revealed protein alterations predominantly in the HIV+ frontal lobe region. The expression of GOLPH3, IMPDH2, DYNLL1, RPL11, and GPNMB proteins was significantly altered in HIV+ frontal lobes compared to that in normal brains. These proteins are associated with metabolic pathways, neurodegenerative disorders, and dementia. These proteomic-level changes may be potential biological markers and therapeutic targets to relieve the dementia-associated symptoms in individuals with HAND.Mayur DokeTamizhselvi RamasamyVaishnavi SundarJay P. McLaughlinThangavel SamikkannuMDPI AGarticleproteomicsSWATHHIV-associated dementiafrontal lobehuman brainLC-MS/MSNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1438, p 1438 (2021)
institution DOAJ
collection DOAJ
language EN
topic proteomics
SWATH
HIV-associated dementia
frontal lobe
human brain
LC-MS/MS
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle proteomics
SWATH
HIV-associated dementia
frontal lobe
human brain
LC-MS/MS
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Mayur Doke
Tamizhselvi Ramasamy
Vaishnavi Sundar
Jay P. McLaughlin
Thangavel Samikkannu
Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
description The chronic irreversible regression of cognitive ability and memory function in human immunodeficiency virus (HIV)-associated dementia (HAND) is linked with late-stage HIV infection in the brain. The molecular-level signatures of neuroinflammation and neurodegeneration are linked with dysfunction in HAND patients. Protein expression changes and posttranslational modification are epigenetic cues for dementia and neurodegenerative disease. In this study quantitative proteome analysis was performed to comprehensively elucidate changes in protein profiles in HIV-positive (HIV+) human brains. Frontal and temporal lobes of normal and HIV+ brains were subjected to label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using the data-independent acquisition method. Comprehensive proteomic identification and quantification analysis revealed that 3294 total proteins and 251 proteins were differentially expressed in HIV+ brains; specifically, HIV+ frontal and temporal lobes had 132 and 119 differentially expressed proteins, respectively. Proteomic and bioinformatic analyses revealed protein alterations predominantly in the HIV+ frontal lobe region. The expression of GOLPH3, IMPDH2, DYNLL1, RPL11, and GPNMB proteins was significantly altered in HIV+ frontal lobes compared to that in normal brains. These proteins are associated with metabolic pathways, neurodegenerative disorders, and dementia. These proteomic-level changes may be potential biological markers and therapeutic targets to relieve the dementia-associated symptoms in individuals with HAND.
format article
author Mayur Doke
Tamizhselvi Ramasamy
Vaishnavi Sundar
Jay P. McLaughlin
Thangavel Samikkannu
author_facet Mayur Doke
Tamizhselvi Ramasamy
Vaishnavi Sundar
Jay P. McLaughlin
Thangavel Samikkannu
author_sort Mayur Doke
title Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
title_short Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
title_full Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
title_fullStr Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
title_full_unstemmed Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes
title_sort proteomics profiling with swath-ms quantitative analysis of changes in the human brain with hiv infection reveals a differential impact on the frontal and temporal lobes
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0ff0bf98961a4dcea3b62196442b2f07
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AT tamizhselviramasamy proteomicsprofilingwithswathmsquantitativeanalysisofchangesinthehumanbrainwithhivinfectionrevealsadifferentialimpactonthefrontalandtemporallobes
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