Weighted gene co-expression network analysis reveals specific modules and biomarkers in Parkinson’s disease

Jin, Xiaojing; Li, Jing; Li, Wei; Wang, Xiao; Du, Chongbo; Geng, Zhangyan; Geng, Yichao; Kang, Lei; Zhang, Xiaoman; Wang, Mingwei; Tian, Shujuan

doi:10.1016/j.neulet.2020.134950

Cited by 16 publications

(14 citation statements)

References 34 publications

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“…12,13,67,67,256 Genomic (new generation sequencing, targeted sequencing, whole exome sequencing, whole genome sequencing), 257 exosomic (30-200 nm nanovesicles with cellstate-specific cargo of proteins, lipids, and nucleic acids), 258,259 epigenetic, 67 and proteomic signatures may help as biomarkers for the early identification of risk at presymptomatic stages. 67,260,261 When clinical symptoms appear, over 60% of midbrain dopaminergic neurons have degenerated and more than 70% of DA levels in striatal synapses are depleted. 262 The treatments available are merely symptomatic, but they are unable to revert dopaminergic neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Since PD‐related neurodegeneration may start decades before the onset of the disease, 255 novel options for presymptomatic diagnosis and prophylactic intervention are necessary 12,13,67,67,256 . Genomic (new generation sequencing, targeted sequencing, whole exome sequencing, whole genome sequencing), 257 exosomic (30–200 nm nanovesicles with cell‐state‐specific cargo of proteins, lipids, and nucleic acids), 258,259 epigenetic, 67 and proteomic signatures may help as biomarkers for the early identification of risk at presymptomatic stages 67,260,261 . When clinical symptoms appear, over 60% of midbrain dopaminergic neurons have degenerated and more than 70% of DA levels in striatal synapses are depleted 262 .…”

Section: Discussionmentioning

confidence: 99%

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Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics

Cacabelos

Carrera

Martínez

et al. 2021

Medicinal Research Reviews

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Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba.Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ ml; and patients chronically treated with anti-PD drugs show an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics

Cacabelos

Carrera

Martínez

et al. 2021

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…The present study aimed to investigate whether lncRNAs play important roles in these pathways via construction of a WGCNA co-expression network, and the results demonstrated that 74 lncRNAs were significantly associated with Th cell-associated pathways, including NR_026691.1. These 74 lncRNAs have similar expression trends to those of genes involved in the Th cell pathway, indicating that they may have the same function (48,49). Thus, these 74 lncRNAs were selected to study the regulatory networks that they may be involved in.…”

Section: Discussionmentioning

confidence: 99%

“…. In addition to chromosomal locations of mRNAs and lncRNAs, the associations between mRNAs and lncRNAs can be analyzed via their expression trends (48,49). WGCNA is a commonly used algorithm for constructing gene co-expression networks by gene expression trends (50).…”

Section: Establishment Of Mrna and Lncrna Co-expression Network Usinmentioning

confidence: 99%

Long non‑coding RNA expression profiles and related regulatory networks in areca nut chewing‑induced tongue squamous cell carcinoma

Zhang

et al. 2020

Oncol Lett

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Areca nut chewing is an important risk factor for developing tongue squamous cell carcinoma (TSCC), although the underlying molecular mechanism is unknown. To determine the potential molecular mechanisms of areca nut chewing-induced TSCC, the present study performed whole-genome detection with five pairs of TSCC and adjacent normal tissues, via mRNA-and long non-coding (lnc)RNA-gene chip analysis. A total of 3,860 differentially expressed genes were identified, including 2,193 lncRNAs and 1,667 mRNAs. Gene set-enrichment analysis revealed that the differentially expressed mRNAs were enriched in chromosome 22q13, 8p21 and 3p21 regions, and were regulated by nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). The results of ingenuity pathway analysis revealed that these mRNAs were significantly enriched for inflammatory immune-related signaling pathways. A co-expression network of mRNAs and lncRNAs was constructed by performing weighted gene co-expression network analysis. The present study focused on NF-κB-, IRF-and Th cell-signaling pathway-related lncRNAs and the corresponding mRNA-lncRNA regulatory networks. To the best of our knowledge, the present study was the first to investigate differential mRNA-and lncRNA-expression profiles in TSCCs induced by areca nut chewing. Inflammation-related mRNA-lncRNA regulatory networks driven by IRFs and NF-κB were identified, as well as the Th cell-related signaling pathways that play important carcinogenic roles in areca nut chewing-induced TSCC. These differentially expressed mRNAs and lncRNAs, and their regulatory networks provide insight for further analysis on the molecular mechanism of areca nut chewing-induced TSCC, candidate molecular markers and targets for further clinical intervention.

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“…There were 38 shared genes between the PD and narcolepsy genesets. CAMK1D is the only gene common among the three genesets for PD, narcolepsy, and IR and it is a Calcium/ Calmodulin kinase that is upregulated in PD patients and is also a risk factor for Type 2 diabetes 22,23 .…”

Section: Keyword Evaluation Of Gene Correlatesmentioning

confidence: 99%

Narcolepsy in Parkinson's disease with insulin resistance

2020

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Background: Parkinson’s disease (PD) is characterized by its progression of motor-related symptoms such as tremors, rigidity, slowness of movement, and difficulty with walking and balance. Comorbid conditions in PD individuals include insulin resistance (IR) and narcolepsy-like sleep patterns. The intersecting sleep symptoms of both conditions include excessive daytime sleepiness, hallucinations, insomnia, and falling into REM sleep more quickly than an average person. Understanding of the biological basis and relationship of these comorbid disorders with PD may help with early detection and intervention strategies to improve quality of life. Methods: In this study, an integrative genomics and systems biology approach was used to analyze gene expression patterns associated with PD, IR, and narcolepsy in order to identify genes and pathways that may shed light on how these disorders are interrelated. A correlation analysis with known genes associated with these disorders (LRRK2, HLA-DQB1, and HCRT) was used to query microarray data corresponding to brain regions known to be involved in PD and narcolepsy. This includes the hypothalamus, dorsal thalamus, pons, and subcoeruleus nucleus. Risk factor genes for PD, IR, and narcolepsy were also incorporated into the analysis. Results: The PD and narcolepsy signaling networks are connected through insulin and immune system pathways. Important genes and pathways that link PD, narcolepsy, and IR are CACNA1C, CAMK1D, BHLHE41, HMGB1, and AGE-RAGE. Conclusions: We have identified the genetic signatures that link PD with its comorbid disorders, narcolepsy and insulin resistance, from the convergence and intersection of dopaminergic, insulin, and immune system related signaling pathways. These findings may aid in the design of early intervention strategies and treatment regimes for non-motor symptoms in PD patients as well as individuals with diabetes and narcolepsy.

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Weighted gene co-expression network analysis reveals specific modules and biomarkers in Parkinson’s disease

Cited by 16 publications

References 34 publications

Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics

Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics

Long non‑coding RNA expression profiles and related regulatory networks in areca nut chewing‑induced tongue squamous cell carcinoma

Narcolepsy in Parkinson's disease with insulin resistance

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