RNA Splicing Dysregulation in Parkinson’s Disease

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.

Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.

This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT.

Relationship Between miRNA and Neurodegenerative Diseases Such as Alzheimer's disease, Parkinson's, Huntington's disease, Amyotrophic Lateral Sclerosis.

The regulatory roles of miRNAs on CNS homeostasis, neuronal differentiation, and synaptic plasticity make these molecules indispensable for healthy brain functions. miRNA dysregulation, by triggering abnormal neurodevelopment, has a critical impact on the etiology and progression of neurodegenerative diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, 18 to 24 nucleotides long. They play a role in posttranscriptional gene regulation by binding to complementary sequences on messenger RNA (mRNA), thereby promoting mRNA degradation or preventing translation into protein. MiRNAs are essential regulators of the genome because they bind targets and alter gene expression. MiRNA biogenesis and functions are tightly regulated, and their dysregulation is associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In particular, disruption of the Blood-Brain Barrier in neurodegenerative diseases allows molecules to leak into the bloodstream, enabling the detection of miRNAs in other body fluids and making these fluids potential biomarker sources. In this context, miRNAs can be measured in blood, cerebrospinal fluid, and other biological samples. It has significant potential for early diagnosis, disease progression monitoring, and evaluation of treatment efficacy. In this review, the relationship between MiRNAs and neuronal degeneration diseases was evaluated. In this review, prepared in light of the current literature scanned through the PubMed database, we examined data from the last 5 years (2021-2026) on neurodegenerative diseases associated with miRNA dysregulation, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD).

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

Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.

A transcriptional framework linking early TDP-43 stress responses to pathological aggregation in AD is provided, and potential upstream therapeutic targets are revealed, including ERK1/2, PI3K, small GTPases, and mRNA splicing pathways.

The Interactions of Tau, RNA, and Stress Granules in Neurodegenerative Disease: A Comprehensive Review

The discovery of RNA in the late 19th century revolutionized the understanding of cell biology. Subsequent discoveries over the next six decades revealed a key role for RNA in protein synthesis. Nevertheless, today, the mechanisms driving RNA metabolism remain enigmatic. Given its fundamental cellular role, RNA alterations are strongly linked to disease, including devastating neurodegenerative disorders pathologically defined by the accumulation of RNA-binding proteins. For example, the mislocalization of TDP-43, an RNA-binding protein, is a pathological feature of amyotrophic lateral sclerosis and frontotemporal dementia TDP-43. Another group of more than 20 neurodegenerative disorders, called tauopathies, is characterized by the aberrant accumulation of the protein tau. Similarly, the emerging concept that tau binds RNA, facilitating the formation of pathological structures, highlights the importance of RNA stability in tauopathies. However, the dynamics and consequences of RNA–tau interactions remain unclear. This review comprehensively catalogs key findings linking tau, RNA, and stress granules. These findings are important because they could offer novel opportunities to design therapeutic strategies.