Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains

Kumar, Narendra; Singh, Vaibhav; Li, Ling; Willard, Belinda; Tripathi, Ajai K.; Dutta, Ranjan

doi:10.3389/fneur.2021.779003

Cited by 6 publications

(1 citation statement)

References 63 publications

(64 reference statements)

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“…Rai et al . 63 reported that VCAN gene expression is associated with the development and function of hypothalamic neurons, especially oligodendrocytes. Also, based on past evidence, dysfunction of oligodendrocyte cells can play a significant role in NOA incidence 64 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a valuable gene network for the diagnosis and treatment of non-obstructive azoospermia: in-silico analyses – experimental research

Zabihi,

Norouzkhani,

Karkhah

et al. 2023

Annals of Medicine &Amp; Surgery

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Introduction: Non-obstructive azoospermia (NOA) is an etiology of infertility in men. NOA may have various classifications; however, Hypogonadotropic hypogonadism can be regarded as a class of NOA associated with genetic factors. Former studies have shown that noncoding RNA (ncRNA) plays an essential role in NOA incidence, but few studies have been performed on the NOA-related ncRNA interaction network. In the current study, genes, NOA-related microRNA (miRNA), and circular RNA (circRNA) were found by bioinformatics methods to offer a new perspective on NOA treatment. Methods: The GnRHR-related protein-protein interaction (PPI) network was extracted by searching in “string-database.” GO, KEGG, and Enrichr databases were used to identify pathways, molecular function, and biological processing. Four Databases, including Target Scan, mirdip, mirmap, and mirwalk were performed to extract miRNAs. At last, the Circ2go, CircBase, and literature were used to identify CircRNAs and their genes. Results: The current study identified the four proteins associated with the GnRHR signaling; eight shared microRNAs that affect the expression of found proteins and 25 CircRNA and their origin genes that regulate the microRNAs’ function. Conclusion: The two miRNAs, hsa-miR-134-3p and hsa-miR-513C-3p, the three genes VCAN, NFATC3, and PRDM5, and their associated CircRNAs can perform as a valuable gene network in the diagnosis and treatment of NOA pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Identification of a valuable gene network for the diagnosis and treatment of non-obstructive azoospermia: in-silico analyses – experimental research

Zabihi,

Norouzkhani,

Karkhah

et al. 2023

Annals of Medicine &Amp; Surgery

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Brain proteome‐wide association study linking‐genes in multiple sclerosis pathogenesis

Jia

Qin

et al. 2022

Ann Clin Transl Neurol

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Objectives To identify genes that confer MS risk via the alteration of cis‐regulated protein abundance and verify their aberrant expression in human brain. Methods Utilizing a two‐stage proteome‐wide association study (PWAS) design, MS GWAS data ( N = 41,505) was respectively integrated with two distinct human brain proteomes from the dorsolateral prefrontal cortex, including ROSMAP ( N = 376) in the discovery stage and Banner ( N = 152) in the confirmation stage. In the following, Bayesian colocalization analysis was conducted for GWAS and protein quantitative trait loci signals to prioritize candidate genes. Differential expression analysis was then used to verify the dysregulation of risk genes in white matter and gray matter for evidence at the transcription level. Results A total of 51 genes whose protein abundance had association with the MS risk were identified, of which 18 genes overlapped in the discovery and confirmation PWAS. Bayesian colocalization indicated six causal genes with genetic risk variants for the MS risk. The differential expression analysis of SHMT1 ( P FDR = 4.82 × 10 −2 ) , FAM120B ( P FDR = 8.13 × 10 −4 ) in white matter and ICA1L ( P FDR = 3.44 × 10 −2 ) in gray matter confirmed the dysregulation at the transcription level. Further investigation of expression found SHMT1 significantly up‐regulated in white matter lesion, and FAM120B up‐regulated in both white matter lesion and normal appearing white matter . ICA1L was down‐regulated in both gray matter lesion and normal appearing gray matter. Interpretation Dysregulation of SHMT1, FAM120B and ICA1L may confer MS risk. Our findings shed new light on the pathogenesis of MS and prioritized promising targets for future therapy research.

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Proteomic networks of gray and white matter reveal tissue‐specific changes in human tauopathy

Johnson,

Dammer,

Webster

et al. 2024

Ann Clin Transl Neurol

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ObjectiveTo define tauopathy‐associated changes in the human gray and white matter proteome.MethodWe applied tandem mass tagged labeling and mass spectrometry, consensus, and ratio weighted gene correlation network analysis (WGCNA) to gray and white matter sampled from postmortem human dorsolateral prefrontal cortex. The sampled tissues included control as well as Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, frontotemporal degeneration with tau pathology, and chronic traumatic encephalopathy.ResultsOnly eight proteins were unique to gray matter while six were unique to white matter. Comparison of the gray and white matter proteome revealed an enrichment of microglial proteins in the white matter. Consensus WGCNA sorted over 6700 protein isoforms into 46 consensus modules across the gray and white matter proteomic networks. Consensus network modules demonstrated unique and shared disease‐associated microglial and endothelial protein changes. Ratio WGCNA sorted over 6500 protein ratios (white:gray) into 33 modules. Modules associated with mitochondrial proteins and processes demonstrated higher white:gray ratios in diseased tissues relative to control, driven by mitochondrial protein downregulation in gray and upregulation in white.InterpretationThe dataset is a valuable resource for understanding proteomic changes in human tauopathy gray and white matter. The identification of unique and shared disease‐associated changes across gray and white matter emphasizes the utility of examining both tissue types. Future studies of microglial, endothelial, and mitochondrial changes in white matter may provide novel insights into tauopathy‐associated changes in human brain.

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Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains

Cited by 6 publications

References 63 publications

Identification of a valuable gene network for the diagnosis and treatment of non-obstructive azoospermia: in-silico analyses – experimental research

Identification of a valuable gene network for the diagnosis and treatment of non-obstructive azoospermia: in-silico analyses – experimental research

Brain proteome‐wide association study linking‐genes in multiple sclerosis pathogenesis

Proteomic networks of gray and white matter reveal tissue‐specific changes in human tauopathy

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