Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson’s disease and insomnia.

Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson’s disease and insomnia.

Publication date: Jan 08, 2025

Parkinson’s disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP metabolism contributes to these conditions remain insufficiently elucidated. This study explores shared tryptophan metabolism-related genes (TMRGs) and molecular mechanisms underlying PD and insomnia, aiming to provide insights into their shared pathogenesis. We analyzed datasets for PD (GSE100054) and insomnia (GSE208668) obtained from the Gene Expression Omnibus (GEO) database. TMRGs were obtained from the Molecular Signatures Database (MSigDB) and the Genecards database. Tryptophan metabolism-related differentially expressed genes (TM-DEGs) were identified by intersecting TMRGs with shared differentially expressed genes (DEGs) from these datasets. Through Protein-Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , and Extreme Gradient Boosting (XGBoost) machine learning, we identified Cytochrome P4501B1 (CYP1B1) and Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, we employed CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) to further investigate the association between hub genes and peripheral immune activation and inflammatory response. Additionally, gene interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, and competing endogenous RNA (ceRNA) networks centered on these hub genes were constructed to explore regulatory mechanisms and potential drug interactions. Finally, validation through bioinformatics and animal experiments identified CYP1B1 as a promising biomarker associated with both PD and insomnia.

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Concepts Keywords
Biomarker Animals
Competing Biomarker
Drug Biomarkers
Gse100054 Biomarkers
Parkinson Gene Expression Profiling
Humans
Insomnia
Mice
Parkinson Disease
Parkinson’s disease
Protein Interaction Maps
Tryptophan
Tryptophan
Tryptophan

Semantics

Type Source Name
pathway KEGG Tryptophan metabolism
disease MESH Parkinson’s disease
disease MESH insomnia
disease MESH neurological disorders
disease MESH tryptophan
drug DRUGBANK L-Tryptophan
pathway REACTOME Metabolism
disease MESH pathogenesis
drug DRUGBANK Flunarizine
drug DRUGBANK Huperzine B
disease MESH interaction Drug
disease MESH neurodegenerative disorder
disease MESH muscle rigidity
disease MESH resting tremor
disease MESH depression
disease MESH Cerebrovascular Diseases
drug DRUGBANK Coenzyme M
pathway KEGG Metabolic pathways
drug DRUGBANK Indole
drug DRUGBANK Serotonin
pathway REACTOME Neurodegenerative Diseases
pathway REACTOME Immune System
disease MESH inflammation
drug DRUGBANK Saquinavir
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH sleep deprivation
drug DRUGBANK Water
drug DRUGBANK Isoflurane
drug DRUGBANK Phosphate ion
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Albendazole
drug DRUGBANK Proline
drug DRUGBANK Isopropyl Alcohol
drug DRUGBANK Formestane
drug DRUGBANK MCC
disease MESH hyposmia
disease MESH cognitive impairment
disease MESH sleep disorder
drug DRUGBANK Melatonin
disease MESH neuroinflammation
disease MESH dysbiosis
disease MESH oxidative stress
drug DRUGBANK Dopamine
drug DRUGBANK Manganese
pathway KEGG Wnt signaling pathway
drug DRUGBANK Ellagic Acid
drug DRUGBANK ZYC300
drug DRUGBANK Aminoglutethimide
drug DRUGBANK Amodiaquine
drug DRUGBANK Toremifene
drug DRUGBANK Naringenin
drug DRUGBANK Anastrozole
drug DRUGBANK Exemestane
drug DRUGBANK Spironolactone
drug DRUGBANK Letrozole
drug DRUGBANK Epirubicin
drug DRUGBANK Rifampicin
drug DRUGBANK Cyclophosphamide
drug DRUGBANK Risperidone
drug DRUGBANK Fluorouracil
pathway KEGG Parkinson disease
disease MESH abnormalities
disease MESH Parkinsonism
disease MESH central nervous system diseases
drug DRUGBANK Quinolinic Acid
disease MESH ischemic stroke
disease MESH COPD
drug DRUGBANK Gold
disease MESH tumor
disease MESH endometriosis
drug DRUGBANK gamma-Aminobutyric acid
pathway REACTOME Inflammasomes
disease MESH breast carcinoma
disease MESH Death
disease MESH cerebral ischemia
disease MESH memory deficits
disease MESH anxiety
disease MESH Electron transfer flavoprotein deficiency
drug DRUGBANK Ethanol
disease MESH mitochondrial dysfunction
disease MESH neuroblastoma
drug DRUGBANK Rotenone
pathway REACTOME Mitophagy
pathway REACTOME Autophagy
pathway REACTOME Methylation
pathway REACTOME Reproduction

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