Integrative Nutrigenomic Systems Biology Analysis of Traditional Chinese Medicine Interventions in Parkinson’s Disease: Nutrient-Gene-Disease Network Perspectives

MicroRNA-phytochemical interactome targeting thioredoxin-interacting protein: a narrative review at the nexus of RNA therapeutics, cancer biology, and metabolic regulation

MicroRNAs (miRNAs) are increasingly recognized as central regulators of gene expression, cellular adaptation, and disease progression. This is fundamentally reshaping current understanding of disease molecular pathogenesis and therapeutic intervention. Beyond their established roles in development and metabolism, miRNAs actively participate in oncogenesis, metabolic dysfunction, inflammation, and redox homeostasis. Emerging evidence shows that phytochemicals can modulate miRNA-mediated regulatory networks by influencing miRNA biogenesis, expression, stability, and functional activity through transcriptional, epigenetic, and post-transcriptional mechanisms. Among these pathways, the thioredoxin-interacting protein (TXNIP) axis has attracted considerable attention because of its critical involvement in oxidative stress, inflammation, metabolic reprogramming, apoptosis, and cancer-associated signalling. For instance, dysregulated TXNIP expression is strongly associated with metabolic dysfunction-associated fatty liver disease (MAFLD), diabetes, cardiovascular diseases, neurodegenerative disorders, and multiple cancers, making it an attractive therapeutic target. This narrative review discussed emerging trends on phytochemical-mediated regulation of TXNIP-associated miRNAs, including miR-148b, miR-33a/b, miR-17-5p, miR-224, and miR-20a. Particular emphasis was placed on the conserved miRNA seed region as the principal determinant of target recognition, while discussing the emerging hypothesis that phytochemicals may allosterically modulate structurally accessible RNA motifs to influence miRNA conformation, stability, RNA-induced silencing complex loading, and target accessibility without disrupting canonical Watson-Crick base pairing. We further discussed molecular docking, RNA-specific molecular dynamics simulations, and complementary structural validation approaches as emerging tools for investigating RNA-ligand interactions. Therefore, this review has provided a mechanistic and translational framework integrating RNA biology, redox signalling, and precision medicine to guide future development of RNA-targeted phytochemical therapeutics for cancer, metabolic disorders, and other chronic diseases.

Systems pharmacology and targeted transcriptional profiling suggest the putative neuroprotective role of Leuconostoc mesenteroides in an in vitro Alzheimer’s disease model

Identification of divergent organ-specific gene and protein expression signatures for mitochondrial function, inflammatory response, and proteostasis in the liver and brain in the rotenone-induced rat model of Parkinson’s disease

Emerging evidence suggests that peripheral organs, particularly the liver, may influence brain homeostasis and neurodegenerative diseases. This study investigates the differential expression of Parkinson’s disease (PD)-related, oxidative stress, and inflammatory genes in the liver and brain of six-week-old male albino Wistar rats (250–300 g) subchronically exposed to rotenone (ROT, 1.3 mg/kg/day, 35 days, b.w.), a pesticide commonly used to model PD. Relative expression levels were measured using quantitative real-time PCR (RT-qPCR) and western blot. Genes involved in mitophagy (Parkin (PARK2), p = 0.0039), oxidative stress response (Parkinson’s disease protein (DJ-1), p = 0.0209), lysosomal function (Low-density lipoprotein receptor-related protein-1 (LRP1), p = 0.0418; ATPase cation transporting 13a2 (ATP13a2), p = 0.0308), and inflammation (Tumour necrosis factor alpha (TNF-α), p = 0.0171) were found upregulated in the brain of ROT-induced rats as compared to control rats, and were also significantly higher than in the liver (p < 0.05). In contrast, significantly higher phosphatase and tensin homolog-induced kinase 1 (PINK1) expression was found in the liver as compared to the brain (p = 0.0198). Notably, these inter-organ differences and transcriptional shifts were absent in the controls. Moreover, the liver exhibited distinct molecular responses, including significant downregulation of ATP13a2 and SNCA (Encoding alpha-synuclein) and overexpression of NFe2-like basic leucine zipper transcription factor 2 (NFe2l2), compared to control rats (p < 0.05). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interferon gamma (IFN-γ) showed no significant changes in either tissue (p > 0.05). These findings demonstrate that distinct molecular alterations in the liver and brain following ROT treatment, including differences in the regulation of genes associated with mitophagy, oxidative stress, proteostasis, and inflammation. Our findings demonstrate tissue-specific molecular associations in the liver and brain within the ROT-induced PD model, providing new insights into the pathophysiology of neurodegeneration and identifying potential biomarkers and therapeutic targets for future studies.

Epigenetic Regulation in Parkinson’s Disease: Cutting -Edge Insights into miRNAs, lncRNAs and Chromatin Modifiers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal aggregation of α-synuclein. While genetic mutations contribute to disease susceptibility, accumulating evidence highlights the pivotal role of epigenetic regulation in modulating gene expression and disease progression. The epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA-mediated regulation, dynamically influence neuronal function, neuroinflammation, mitochondrial homeostasis, and protein aggregation in Parkinson’s disease. Recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are critical regulators of α-synuclein expression, dopaminergic neuron survival, and inflammatory signaling pathways. In parallel, chromatin modifiers such as histone acetyltransferases and deacetylases orchestrate transcriptional programs that determine neuronal vulnerability and resilience. The intricate crosstalk among miRNAs, lncRNAs, and chromatin-modifying complexes underscores the complexity of epigenetic networks in PD pathogenesis. Furthermore, epigenetic alterations have emerged as promising biomarkers for early diagnosis and disease monitoring, as well as attractive therapeutic targets for disease-modifying interventions. Advances in epigenetic-based therapies, including histone deacetylase inhibitors and RNA-based strategies, offer new opportunities for precision medicine in Parkinson’s disease. This review critically summarizes current insights into the roles of miRNAs, lncRNAs, and chromatin modifiers in Parkinson’s disease, discusses their potential as biomarkers and therapeutic targets, and highlights key challenges and future perspectives in translating epigenetic discoveries into clinical applications.

Integrative Multi-Omics Analysis Reveals Convergent Epigenome and Transcriptome Changes in Parkinson's Disease.

BACKGROUND The mechanisms that predispose dopaminergic neurons (DAN) to degeneration in Parkinson's disease (PD) are incompletely understood. OBJECTIVE To perform an integrative multi-omics reanalysis of single-cell transcriptomic and epigenomic data to identify convergent alterations predisposing dopaminergic neurons to degeneration in Parkinson's disease, and to generate new bulk ATAC-seq profiles from peripheral monocytes to assess whether these alterations extend to a systemic, cross-tissue epigenetic signature. METHODS We reanalyzed single-cell RNA sequencing (scRNA-seq; n = 27 PD, 11 controls) and single-cell ATAC sequencing (scATAC-seq; n = 10 PD, 2 controls) data from induced pluripotent stem cell (iPSC)-derived DANs (Foundational Data Initiative for Parkinson's Disease [FOUNDIN-PD]) to identify convergent transcriptional and epigenetic alterations. We generated new bulk ATAC-seq from peripheral monocytes of parkinsonian disorder patients (n = 10) and controls (n = 4) to assess cross-tissue epigenetic signatures. RESULTS Convergent downregulation in neurodevelopmental and synaptic pathways was observed across neuronal maturation stages. Network perturbation analysis identified SMARCA4 as a key upstream regulator. Monocyte comparison revealed 44 genes with concordant chromatin accessibility changes, with NFATC2 exhibiting decreased accessibility across all neuronal subtypes and monocytes. CONCLUSION This exploratory analysis identifies shared transcriptomic-epigenomic alterations at gene, pathway, and network levels in PD neurons and preliminary systemic epigenetic signatures that warrant validation in larger cohorts. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Genetic and epigenetic complexity of Parkinson's disease: From dopamine pathways to estrogen interplay.