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

Epigenetic modulators as therapeutics for neurodegenerative disorders/Alzheimer's disease.

Overall, epigenetic modulators present a promising therapeutic approach for neurodegeneration, and continued research integrating various assays like DNA methylation analysis, histone modification analysis, non-coding RNA analysis, neuroinflammation analysis, and functional and behavioral assays in AD models is significant in harnessing the full potential for AD treatment.

RNA Splicing Dysregulation in Parkinson’s Disease

Current evidence on the RNA regulatory networks in PD is examined, highlighting the role of transcript isoforms and RBPs in neuronal dysfunction and emerging data suggest that dysregulation of RNA binding proteins (RBPs) may influence RNA processing in PD.

Mitochondria in Parkinson disease: Genetic and epigenetic components

This review aims to elucidate the genetic and epigenetic mechanisms underlying mitochondrial dysfunction in Parkinson’s disease (PD) and to explore how these insights inform emerging therapeutic strategies. A comprehensive analysis of current literature was conducted to integrate evidence on mitochondrial homeostasis, mitophagy regulation, and genome stability, with a focus on mutations in SNCA, LRRK2, VPS35, PINK1, PARK2, DJ-1, and POLG, as well as epigenetic alterations affecting mitochondrial DNA. Genetic mutations disrupt mitochondrial dynamics, impair autophagy, and cause oxidative stress, leading to dopaminergic neuron degeneration. Epigenetic modifications—such as altered DNA methylation, histone acetylation, and non-coding RNA regulation—further exacerbate mitochondrial instability and neuronal apoptosis. Mitochondrial impairment represents a common denominator linking hereditary and sporadic forms of PD, providing a unifying model of disease pathogenesis. Advances in understanding mitochondrial biology have enabled the development of novel therapeutic approaches, including activators of the PINK1/Parkin pathway, inhibitors of LRRK2 and α-synuclein aggregation, and strategies promoting mitochondrial biogenesis and intercellular transfer, offering potential for disease modification.

Epigenetic dysregulation in depression: molecular mechanisms, clinical biomarkers, and therapeutic opportunities

Major depressive disorder (MDD) is a widespread, recurrent, and severely disabling psychiatric disorder that imposes a heavy global health burden. Although genetic factors contribute to disease risk, growing evidence highlights gene-environment interaction as the core driver of MDD pathogenesis. Epigenetic regulation acts as a precisely molecular interface that translates environmental stressors into stable changes in gene expression and long-term behavioral phenotypes. In this review, we provide a comprehensive and up-to-date overview of epigenetic dysregulation in MDD, covering five major regulatory layers: DNA methylation, histone post-translational modifications, non-coding RNA networks, RNA chemical modifications, and ATP-dependent chromatin remodeling. We emphasize the spatiotemporal specificity, brain regional selectivity, and cell-type. dependency of these epigenetic events, and their roles in disrupting neuroplasticity, hypothalamic–pituitary–adrenal (HPA) axis function, neurotransmitter homeostasis, and neuroinflammation. We further evaluate the translational value of peripheral epigenetic markers for early diagnosis, severity monitoring, and prediction of antidepressant treatment responses. We also discuss emerging epigenetic-targeted therapeutic strategies, including small-molecule inhibitors, RNA-based modulators, and brain-targeted delivery systems. Finally, we address key obstacles to clinical translation, such as tissue heterogeneity, unclear causality, limited reproducibility, and lack of standardized protocols. We propose future directions centered on single-cell multi-omics, longitudinal clinical validation, and sex-and ethnicity-stratified research. This review aims to establish an integrated framework for understanding MDD epigenetics and accelerating the development of precision diagnostic and therapeutic approaches.

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.

Circular RNAs orchestrate molecular networks in osteoarthritis: From miRNA sponging to epigenetic and exosome-mediated regulation