Neural Tube Defects: From a Proteomic Standpoint

Puvirajesinghe, Tania M.; Borg, Jean-Paul

doi:10.3390/metabo5010164

Cited by 8 publications

(7 citation statements)

References 98 publications

(118 reference statements)

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“…In the past decades, NTD-relevant studies have been done from a transcriptome, metabolomics, and proteomics perspective ( Fan et al, 2011 ; Hansler et al, 2014 ; Liu et al, 2014 ; Puvirajesinghe and Borg, 2015 ; Yu et al, 2017 ; Wang et al, 2022 ). In transcriptomic profiles at embryonic days (E) 8.5, 9.5 and 10.5 d in a retinoic acid-induced NTD model, Yu et al, found that genes such as Bmp2, Ascl1, Olig2, Lhx1, Wnt7b, Eomes, Foxp2, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Tbx20, Nfib, Cntn1, Dcx, Gpr56, Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan, App, Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3, and Rbfox1 were differentially expressed during mouse neural tube development ( Yu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs

Pei,

Shen,

et al. 2024

Front. Cell Dev. Biol.

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Introduction: In the early stage of embryonic development, the neural tube (NT) cannot be closed properly due to some complex factors, including environmental factors, genetic factors, and the relationship between various factors, leading to the occurrence of neural tube defects (NTDs).Methods: In this study, we induced a mouse model of NTDs by feeding mice with a low-folate diet and intraperitoneally injecting them with 1.5 mg/kg methotrexate on E7.5. Fetal mice were achieved at E13.5, and we extracted proteins from brain tissues with trypsin digestion. After enzymatic digestion, peptides were labeled with TMT/iTRAQ and separated in high-performance liquid chromatography (HPLC) for subsequent liquid chromatography tandem mass spectroscopy (LC-MS/MS) analysis. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation to analyze proteomic changes and analyze the functional enrichment of differentially expressed proteins (DEPs) in the NTD mice tissues.Results: A low-folate-induced mouse model was successfully constructed. Folate was used as a sensitizing agent, and the teratogenicity rate of the NTD fetal mice increased to 36.5% when the concentration of methotrexate was at 1.5 mg/kg. Mass spectrometry was used to identify 6,614 proteins, and among them, 5,656 proteins were quantified. In the following proteomic analysis, GO classification and KEGG pathway enrichment analysis were conducted, and heatmaps were drawn for differentially expressed proteins (DEPs). The main pathways associated with NTDs, such as the Hedgehog, Wnt, p53, and Hippo signaling pathways and the one-carbon pool mediated by folate, can be identified through a protein–protein interaction (PPI) network. It was also found that the regulation of ribosomal proteins, such as RPL13 and RPL14, which are upregulated in NTDs, has a certain impact on neural tube development.Discussion: Our results revealed proteomic changes in the tissues of low-folate-induced NTD mice. Validation showed that ribosomal proteins play a regulatory role during the development of NTDs and provides new ideas for the pathogenesis and preventive measures of NTDs.

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Section: Discussionmentioning

confidence: 99%

Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs

Pei,

Shen,

et al. 2024

Front. Cell Dev. Biol.

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“…Among the above variables, a i > 0 is the Lagrange multiplier. The maximum value of function ( 4) is obtained for a i under the constraint condition of (5).…”

Section: Pca Data Analysis and Svm Model Establishmentmentioning

confidence: 99%

“…3 Genetic studies have shown that NTDs constitute a polygenic class of diseases that have been found to be affected by numerous undefined receptors and cytoplasmic signaling molecules encoded by multiple genes. 5 Recent discoveries have implicated the classical complement cascade to be involved in normal brain development and disease. 6 Complement factors also function to guide postmitotic cells to their final doi: 10.1111/nyas.14443 destinations in both the peripheral and CNS.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, environmental teratogens that have been associated with NTDs include the anticonvulsant drug valproic acid, the fungal product fumonisin, and other nongenetic risk factors 3 . Genetic studies have shown that NTDs constitute a polygenic class of diseases that have been found to be affected by numerous undefined receptors and cytoplasmic signaling molecules encoded by multiple genes 5 …”

Section: Introductionmentioning

confidence: 99%

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Complement factors and alpha‐fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects

Dong

Liú

et al. 2020

Annals of the New York Academy of Sciences

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Neural tube defects (NTDs) are serious congenital malformations. In this study, we aimed to identify more specific and sensitive maternal serum biomarkers for noninvasive NTD screenings. We collected serum from 37 pregnant women carrying fetuses with NTDs and 38 pregnant women carrying normal fetuses. Isobaric tags for relative and absolute quantitation were conducted for differential proteomic analysis, and an enzyme-linked immunosorbent assay was used to validate the results. We then used a support vector machine (SVM) classifier to establish a disease prediction model for NTD diagnosis. We identified 113 differentially expressed proteins; of these, 23 were either upor downregulated 1.5-fold or more, including five complement proteins (C1QA, C1S, C1R, C9, and C3); C3 and C9 were downregulated significantly in NTD groups. The accuracy rate of the SVM model of the complement factors (including C1QA, C1S, and C3) was 62.5%, with 60% sensitivity and 67% specificity, while the accuracy rate of the SVM model of alpha-fetoprotein (AFP, an established biomarker for NTDs) was 62.5%, with 75% sensitivity and 50% specificity. Combination of the complement factor and AFP data resulted in the SVM model accuracy of 75%, and receiver operating characteristic curve analysis showed 75% sensitivity and 75% specificity. These data suggest that a disease prediction model based on combined complement factor and AFP data could serve as a more accurate method of noninvasive prenatal NTD diagnosis.

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“…The central nervous system starts to develop in the third week of gestation [1][2][3]. Vertebrae develop from somites, and they are formed rhythmically and sequentially through a process called somitogenesis.…”

Section: Introductionmentioning

confidence: 99%

Congenital malformations in the vertebral column: associations and possible embryologic origins

et al. 2022

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Cases of associations between random spinal congenital defects have previously been reported, yet several questions remain unanswered. Firstly, why are associations between what seems to be random combinations of vertebral malformations observed? Secondly, is there a common event or pattern that connects the associated defects? Therefore, this study aimed to identify congenital defects in the vertebral column and also to determine whether any associations, if present, between vertebral malformations exist. This article consequently discusses the possible embryological disruptions that may lead to the formation of various defects in the vertebral column. A random skeletal sample (n=187) was selected from the Pretoria Bone Collection housed in the Department of Anatomy, University of Pretoria (Ethics 678/2018). The sample was evaluated to determine the frequencies of spinal congenital defects in each set of remains. Identifiable congenital malformations were observed in 48.1% (n=90/187) of the sample. The results demonstrated a high probability of association between the different defects observed in the vertebral column. Findings are of value as they provide a reasonable explanation to why seemingly random cases of associations have been reported by several authors. This study is clinically relevant as severe spinal defects have been shown to have high morbidity in patients and mortality in infants.

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Neural Tube Defects: From a Proteomic Standpoint

Cited by 8 publications

References 98 publications

Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs

Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs

Complement factors and alpha‐fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects

Congenital malformations in the vertebral column: associations and possible embryologic origins

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