Effects of Intron 1 Sequences on Human <i>PLP1</i> Expression: Implications for <i>PLP1</i>-Related Disorders

Wight, P.A.L.

doi:10.1177/1759091417720583

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…Consequently, TM4SF1, TNFSF10, and PLP1 were identified, in which only PLP1 was significantly upregulated as verified by RT-qPCR. PLP1 is the most abundant protein of myelination (Eng et al, 1968;Norton and Poduslo, 1973;Wight, 2017), and the mutation of PLP1 can lead to the X-chromosome-linked leukodystrophy Pelizaeus-Merzbacher disease (Elitt et al, 2020). PLP1 has been widely reported in the formation of the central nervous system while the aberrant expression of PLP1 in various malignant tumors was identified by the bioinformatic analysis (Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Our result suggested that the hypomethylation of PLP1 might be involved in the pathophysiology of UFs, but further experiments still need to implement. Moreover, overexpressed PLP1 exhibited major oxidative phosphorylation deficits ( Wight, 2017 ) and the down-regulation of oxidative phosphorylation aggravates therapeutically adverse tumor hypoxia ( Ashton et al, 2018 ). According to our result that the 22 DEGs including PLP1 were enriched in hypoxia, we constructed the posits that PLP1 might participate in the hypoxia program to onset the fibroids.…”

Section: Discussionmentioning

confidence: 99%

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PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

Cai

Liao²,

Li³

et al. 2022

Front. Genet.

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Objective: We aim to identify the crucial genes or potential biomarkers associated with uterine fibroids (UFs), which may provide clinicians with evidence about the diagnostic biomarker of UFs and reveal the mechanism of its progression.Methods: The gene expression and genome-wide DNA methylation profiles were obtained from Gene Expression Omnibus database (GEO). GSE45189, GSE31699, and GSE593 datasets were included. GEO2R and Venn diagrams were used to analyze the differentially expressed genes (DEGs) and extract the hub genes. Gene Ontology (GO) analysis was performed by the online tool Database for Annotation, Visualization, and Integrated Discovery (DAVID). The mRNA and protein expression of hub genes were validated by RT-qPCR, western blot, and immunohistochemistry. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value.Results: We detected 22 DEGs between UFs and normal myometrium, which were enriched in cell maturation, apoptotic process, hypoxia, protein binding, and cytoplasm for cell composition. By finding the intersection of the data between differentially expressed mRNA and DNA methylation profiles, 3 hub genes were identified, including transmembrane 4 L six family member 1 (TM4SF1), TNF superfamily member 10 (TNFSF10), and proteolipid protein 1 (PLP1). PLP1 was validated to be up-regulated significantly in UFs both at mRNA and protein levels. The area under the ROC curve (AUC) of PLP1 was 0.956, with a sensitivity of 79.2% and a specificity of 100%. Conclusion: Overall, our results indicate that PLP1 may be a potential diagnostic biomarker for uterine fibroids.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

Cai

Liao²,

Li³

et al. 2022

Front. Genet.

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“…PLP is important for communication between oligodendrocytes and axons served a neuroprotective role. It is required for proper sequestration of proteins into the myelin compartment, allegedly important for axo-glial metabolism and long-term support of axon [38]. Plp-null mice exhibited severe early-onset thermal hyperalgesia, in the absence of thermal allodynia with late onset central demyelination [39].…”

Section: Discussionmentioning

confidence: 99%

Activation of spinal ephrin‐B3/EphBs signaling induces hyperalgesia through a PLP‐mediated mechanism

Zhang

Qiao

Shu

et al. 2021

Fundamemntal Clinical Pharma

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Ephrin B/EphB signaling pathway is involved in the regulation of pain caused by spinal cord injury. However, the role of ephrin-B3/EphBs signaling in regulation of nociceptive information is poorly understood. In the present study, formalin-induced inflammatory pain, mechanical allodynia and thermal hyperalgesia, was measured using Efnb3 mutant mice (Efnb3 À/À ) and wild-type (Efnb3 +/+ ) mice. The spinal cord (L4-6) was selected for molecular and cellular identification by western blotting and immunofluorescence. Efnb3 mutant mice showed a significant increased the thermal and mechanical threshold, followed by aberrant thin myelin sheath. Furthermore, expression of proteolipid protein (PLP) was significantly lower in L4-6 spinal cord of Efnb3 À/À mice. These morphological and behavioral abnormalities in mutant mice were rescued by conditional knock-in of wild-type ephrin-B3. Intrathecal administration of specific PLP siRNA significantly increased the thermal and mechanical threshold hyperalgesia in wild-type mice. However, overexpressing PLP protein by AAV9-PLP could decrease the sensitivity of mice to thermal and mechanical stimuli in Efnb3 À/À mice, compared with scrabble Efnb3 À/À mice. Further, Efnb3 lacz mice, which have activities to initiate forward signaling, but transduce reverse signals by ephrin-B3, shows normal acute pain behavior, compared with wild type mice. These findings indicate that a key molecule Efnb3 act as a prominent contributor to hyperalgesia and essential roles of ephrin-B3/EphBs in nociception through a myelin-mediated mechanism.Eph/ephrin receptor is currently the largest family of tyrosine kinase receptors, divided into two subfamilies, A and B, which form high-affinity protein by binding to ephrin A and ephrin B ligands, respectively [1]. Both the Eph receptor and the ephrin ligand are anchored on the surface of the cell, and ephrin A has only the extracellular region, which is directly anchored to the cell membrane by a glycosyl group, whereas ephrin B has a hydrophobic transmembrane region and intracellular region, which can transmit intracellular signals through

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“…The idea that PLP1 might have more than a structural role was understood after it was known that the Plp1 gene was active long before the beginning of myelination [ 46 , 61 ]. In addition, Plp1 gene products have been detected in CNS non-myelinating cells, for instance, in olfactory ensheathing cells [ 62 ], brainstem neurons [ 63 ], cerebellum, and hippocampus neurons [ 64 ], and satellite cells [ 65 ]. Furthermore, neuronal PLP isoforms have been detected during human fetal development that is addressed as classical PLP proteins to the plasma membrane [ 66 ].…”

Section: Proteolipid Protein 1: Substantial Physiological Functionsmentioning

confidence: 99%

Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia

Khalaf

Mattern²,

Bégou

et al. 2022

Biomedicines

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Pelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 (PLP1) gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the PLP1 gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases.

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Effects of Intron 1 Sequences on Human PLP1 Expression: Implications for PLP1-Related Disorders

Cited by 8 publications

References 52 publications

PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

Activation of spinal ephrin‐B3/EphBs signaling induces hyperalgesia through a PLP‐mediated mechanism

Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia

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