Integrated bioinformatics analysis for exploring potential biomarkers related to Parkinson’s disease progression

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 17, 2024

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative with increasing prevalence. Effective diagnostic markers and therapeutic methods are still lacking. Exploring key molecular mechanisms for PD can help early diagnosis treatment improvement. Methods Three datasets GSE174052, GSE77668, GSE168496 were obtained from the GEO database to search differentially expressed circRNA (DECs), miRNAs (DEMis), mRNAs (DEMs). GO KEGG enrichment analyses, protein–protein interaction (PPI) network construction implemented explore possible actions of DEMs. Hub genes selected establish circRNA-related competing endogenous RNA (ceRNA) networks. Results There 1005 downregulated DECs, 21 upregulated DEMis, 266 234 DEMs identified. The significantly enriched in various PD-associated functions pathways such as extracellular matrix organization, dopamine synthesis, PI3K-Akt, calcium signaling pathways. Twenty-one hub screened out, PD-related ceRNA regulatory was constructed containing 31 circRNAs, one miRNA (miR-371a-3p), gene ( KCNJ6 ). Conclusion We identified networks, providing new directions treatment.

Language: Английский

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Neuroprotective and anti-inflammatory effects of the RIPK3 inhibitor GSK872 in an MPTP-induced mouse model of Parkinson’s disease

Neurochemistry International, Journal Year: 2024, Volume and Issue: 181, P. 105896 - 105896

Published: Nov. 2, 2024

Language: Английский

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Wnt1 oversees microglial activation by the Wnt/LRP5/6 receptor signaling pathway during lipopolysaccharide-mediated toxicity

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 1, 2025

Abstract Background The protective effects of autophagy-mediated microglial inflammatory regulation on diseases the central nervous system (CNS) has been a recent field interest. canonical signaling pathway activated by Wnt1, Wnt/β-catenin cascade, also plays crucial role in neurodegenerative diseases. However, relationship between Wnt1/β-catenin and activation remains unclear. Our study focused understanding impact mechanism Wnt1 activation. Methods results To simulate neuroinflammatory conditions vitro, BV2 cells were exposed to 1 μg/mL lipopolysaccharide. CD86- CD206-positive identified flow cytometry immunofluorescence assays. Inflammatory anti-inflammatory factors measured using enzyme-linked immunosorbent Autophagy was analyzed expression LC3B puncta, LC3, P62, beclin1 expression. suppressed rhWnt1 restricted DKK1, siRNA-β-catenin siRNA-LKB1, respectively, with concomitant changes β-catenin phosphorylation NFκB-p65, LKB1, AMPK. Although effect Wnt1/LKB1 independent β-catenin, regulated β-catenin. reduced inflammation caused is linked its enhancement autophagy, process blocked siRNA-LKB1 3-MA partially. Conclusions improved partly dependent or LKB1. Furthermore, independently participated regulating research unveils previously unknown method through which exerts effects, may have potential against CNS

Language: Английский

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The interplay between α-synuclein aggregation and necroptosis in Parkinson’s disease: a spatiotemporal perspective

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 8, 2025

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the death of dopaminergic neurons and aggregation alpha-synuclein (α-Syn). It presents with prominent motor symptoms, time diagnosis, significant number have already been lost. Current medications can only alleviate symptoms but cannot halt progression. Studies confirmed that both neuronal loss α-Syn are associated necroptosis mechanisms. Necroptosis, regulated form cell death, has recognized as an underexplored hotspot in PD pathogenesis research. In this review, we propose spatiotemporal model progression, highlighting interactions between aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation necroptosis. These processes not drive also contribute to early non-motor offering insights into potential diagnostic markers. Finally, touch upon therapeutic inhibition enhancing current treatments, such L-Dopa. This review aims provide new perspective on identify avenues for development more effective strategies.

Language: Английский

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An integrated bioinformatics and machine learning approach to identifying biomarkers connecting parkinson’s disease with purine metabolism-related genes

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 16, 2025

Language: Английский

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Construction and Identification of Inflammation‐Related TF–mRNA–miRNA Coexpression Network and Immune Infiltration in Parkinson’s Disease

Parkinson s Disease, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Parkinson’s disease (PD) is the second most common neurodegenerative worldwide. Inflammation, marked by infiltration of inflammatory mediators and proliferation cells, closely linked to PD. This study aims identify validate inflammation‐related biomarkers in PD construct a TF–mRNA–miRNA coexpression network through bioinformatics analysis. Methods: The PD‐associated dataset GSE7621 genes were downloaded from GEO Database GeneCards platform obtain differential expression (IRDEGs). key IRDEGs generated PPI gene levels validated blood samples patients using QPCR We utilized ENCODE, hTFtarget, CHEA, miRWALK, miRDB databases upstream downstream molecular models for constructing interaction IRDEGs. Finally, based on CIBERSORT algorithm, associations between IRDEs immune cell investigated. Results: A total four (CXCR4, LEP, SLC18A2, TAC1) screened validated. Through biological function analysis, key‐related pathways networks identified. These may be related onset Additionally, we found that increased CD4 T‐cell might associated with occurrence Conclusions: identified potential treatment target constructed regulatory network. information provides an initial basis understanding complex mechanisms.

Language: Английский

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Identification of biomarkers associated with inflammatory response in Parkinson’s disease by bioinformatics and machine learning

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(5), P. e0320257 - e0320257

Published: May 28, 2025

Parkinson’s disease (PD) is a common and debilitating neurodegenerative disorder. The inflammatory response essential in the pathogenesis progression of PD. goal this study to combine bioinformatics machine learning screen for biomarker genes related First, differentially expressed associated with were screened, PPI networks constructed enriched analysis. LASSO, SVM-RFE Random Forest algorithms used genes. Then, ROC curves drawn PD risk predicting models on basis Finally, drug sensitivity analysis, mRNA-miRNA network construction single-cell transcriptome data analysis performed. experimental results showed that we screened 31 response. Signaling pathways such as cytokine activity these Three biomarkers identified using algorithms: IL18R1, NMUR1 RELA. Seventeen co-associated miRNAs by possible regulatory nodes three found be closely T cells, Endothelial excitatory neurons, inhibitory other cells transcriptomic In conclusion, RELA could potential therapeutic targets new diagnosis.

Language: Английский

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Early concentrate starter introduction induces rumen epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities the ruminal stratified squamous keratinization process, negatively impacts ruminant health and performance. However, we still lack comprehensive perception of underlying mechanisms predisposing factors for this disorder. Here, investigated rumen cell heterogeneity, differentiation trajectories, cornification to clarify process discern key metabolites contributing parakeratosis. Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, plus alfalfa hay corn-soybean concentrate starter feeding. At 42 days age, slaughtered, tissues collected single-cell RNA-sequencing (scRNA-seq), immunofluorescence, quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples metabolomic organoid was used verify As expected, observed that introduction resulted Moreover, scRNA-seq analysis revealed developmental impediment transition from differentiated keratinocytes terminally (TDK) with introduction. Immunofluorescence qRT-PCR analyses further verified location expression marker genes TDK. Metabolomic showed robust positive correlation between butyrate levels keratinization. More importantly, successfully established model capable facilitating study epithelia confirmed high dose indeed contributed Collectively, induces parakeratosis blocking keratinocyte excessive accumulation neonatal lamb model. These findings enhance our understanding provide valuable insights addressing using early nutritional intervention strategies.

Language: Английский

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Die hard: necroptosis and its impact on age-dependent neuroinflammatory diseases

Frontiers in Cell Death, Journal Year: 2024, Volume and Issue: 3

Published: March 8, 2024

The pro-inflammatory form of cellular death, necroptosis, is critical to age-related pathologies. Necroptosis primarily functions as an antipathogenic and antitumor biological mechanism by triggering inflammatory pathways within rogue cell bodies, resulting in death. Several neurodegenerative conditions have hallmarks suggesting a potential role for this death pathway the pathogenesis neuroinflammation neuronal likely through release cytokines that perpetuate signaling neurodegeneration. receptor-interacting protein kinases 1 3 (RIPK1/3) cascade necroptosis regulation; however, complete behind necroptotic activation, regulation, resolution remains incomplete. In cases where disadvantageous, such diseases, we lack effective pharmacological suppressors could mitigate disease progression. Targeting regulatory proteins has shown promise; need specific inhibitors limits therapeutic opportunities. This review focuses on its neurodegeneration age-dependent disorders. We comprehensively detail known partners discuss ongoing efforts targeting preventing active their relevance neuroprotection.

Language: Английский

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Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6215 - 6215

Published: June 5, 2024

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure air pollutants can occur during breathing, posing a considerable risk those environmental health vulnerabilities. Among vulnerable individuals, maternal exposure negatively impact the mother and child in utero. The developing fetus is particularly substances, potentially greater implications. pollutants, toluene neurotoxic, its effects widely explored. However, of low-level daily life remains unclear. Herein, we evaluated 194 mothers infants from Growing children’s Evaluation Environment (GREEN) cohort determine possible early-life on nervous system. Using Omics experiments, were confirmed based epigenetic changes altered mRNA expression. Various identified, upregulated expression contributing diseases such as glioblastoma Alzheimer’s, downregulated being structural neuronal abnormalities. These findings detected both infant groups, suggesting fetus. Our will facilitate establishment policies, including management for groups.

Language: Английский

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