Identification of potential diagnostic biomarkers for Parkinson's disease

Feng-hua, Jiang; Wu, Qianqian; Sun, Shumin; Bi, Guang-Hui; Guo, Ling

doi:10.1002/2211-5463.12687

Cited by 40 publications

(29 citation statements)

References 28 publications

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“…In general, expression levels of inflammatory factors are increased in the peripheral blood of PD patients. Nevertheless, essential T lymphocyte activation genes have also been found to be decreased in the reports of Jiang et al, Chi et al and Calligaris et al 16,83,84 . It is tempting to speculate that this may be attributed to the increased Treg activity, which was demonstrated by our study.…”

Section: Discussionmentioning

confidence: 91%

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Karaaslan

Kahraman

Şanlı

et al. 2021

Sci Rep

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Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein–protein interaction analyses were performed with STRING. Expression levels of randomly selected DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in PBMC. A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the effort of the immune system to suppress ongoing neuroinflammation.

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Section: Discussionmentioning

confidence: 91%

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Karaaslan

Kahraman

Şanlı

et al. 2021

Sci Rep

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“…It was reported that lncRNAs play essential roles in the pathogenesis of PD via regulating gene expression Liu and Lu, 2018;Xu et al, 2018). Several studies reported altered mRNA expression profiles of PD blood samples (Scherzer et al, 2007;Jiang et al, 2019). One advantage of our study is that we simultaneously profiled both of the lncRNA and mRNA expression in circulating leukocytes from the same PD patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated Long Non-coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells

Fan

Yang

et al. 2019

Front. Neurosci.

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The molecular mechanism underlying Parkinson's disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human diseases. We hypothesize that lncRNAs are involved in neuronal degeneration of PD. Using microarray, we identified 122 differentially expressed (DE) lncRNAs and 48 DE mRNAs between the circulating leukocytes from PD patients and healthy controls. There were 714 significant correlations (r ≥ 0.8 or ≤−0.8, p < 0.05) among the DE lncRNAs and mRNAs. Gene function and pathway analysis of the 48 DE mRNAs revealed biological pathways related to PD pathogenesis, including immune response, inflammatory response, MAPK, and Jak-STAT pathway. In a cohort of 72 PD patients and 22 healthy controls, the upregulation of four lncRNAs (AC131056.3-001, HOTAIRM1, lnc-MOK-6:1, and RF01976.1-201) in circulating leukocytes of PD patients were further confirmed. These lncRNAs were also upregulated in THP-1 cells, a human monocytic cell line, after inflammatory stimulation. Interestingly, the conditioned culture medium of THP-1 cells or 6-OHDA significantly increased the expression of these lncRNAs in SH-SY5Y cells, a human neuroblastoma cell line expressing dopaminergic markers. Importantly, overexpression of AC131056.3-001 or HOTAIRM1 increased baseline and 6-OHDAinduced apoptosis of SH-SY5Y cells. Taken together, we identified distinct expression profiles of lncRNA and mRNA in circulating leukocytes between PD patients and healthy controls. Dysregulated lncRNAs such as HOTAIRM1 and AC131056.3-001 may contribute to PD pathogenesis by promoting the apoptosis of dopaminergic neuron.

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“…This data concurs with the fact that as in the case of the old age group, PD patients are not able to regulate inflammation as effectively as healthy individuals. LRRN3 has recently been reported as a potential biomarker of PD [28]. CHGB encodes a tyrosine-sulfated secretory protein abundant in neurons.…”

Section: Discussionmentioning

confidence: 99%

A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson’s disease

et al. 2019

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Parkinson’s disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.

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Identification of potential diagnostic biomarkers for Parkinson's disease

Cited by 40 publications

References 28 publications

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Dysregulated Long Non-coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells

A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson’s disease

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