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.
Sumithira George, Sivakumar Subramaniyan, Mukesh Rajagopal et al.· Scholars Journal of Applied...· 0 citations
Alzheimer's disease (AD) is the leading cause of dementia worldwide, accounting for approximately 60–70% of all dementia cases. It is a progressive neurodegenerative disorder that results in memory loss, cognitive decline and functional impairment, and affects over 55 million individuals worldwide. The number of affected individuals is projected to reach 139 million by 2050, posing a substantial public health and socioeconomic burden. Pathologically, AD is defined by extracellular deposits of amyloid-β (Aβ) plaques and intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles (NFTs). There is growing evidence that the pathogenesis of AD is multifactorial, involving genetic, molecular, and environmental factors. This review aims to give a comprehensive overview of the major genes and molecular pathways involved in the pathogenesis of AD, as well as recent advances in genome-wide association studies (GWAS) and emerging therapeutic strategies. The mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1), presenilin 2 (PSEN2), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) are associated with early-onset familial AD, while late-onset AD is linked to several susceptibility genes identified by GWAS. The molecular mechanisms underlying AD pathogenesis and progression are discussed with respect to major AD-associated genes, such as microtubule-associated protein tau (MAPT), apolipoprotein E (APOE), triggering receptor expressed on myeloid cells 2 (TREM2), sortilin-related receptor 1 (SORL1), bridging integrator 1 (BIN1), phosphatidylinositol-binding clathrin assembly protein (PICALM), Clusterin (CLU), ATP-binding cassette subfamily A member 7 (ABCA7), complement receptor 1 (CR1), acetylcholinesterase (AChE), nuclear factor erythroid 2-related factor 2 (NRF2), and tumor necrosis factor (TNF). Current therapeutic strategies, including anti-amyloid immunotherapy, AChE inhibitors, tau-directed therapies, and emerging gene-targeted approaches, are also discussed. In addition, progress in multi-omics technologies, disease models using induced pluripotent stem cells (iPSC), gene editing with CRISPR-Cas9, and artificial intelligence (AI) analysis are likely to speed up the implementation of precision medicine for early diagnosis, risk prediction, and treatment of Alzheimer's disease.
Sumithira George, Sharan Kumar, Sivakumar Subramaniyan et al.· Middle East Research Journal...· 0 citations