Epigenetic reprogramming as a therapeutic strategy for neurodegenerative diseases: A complex and novel approach

Epigenetic reprogramming has emerged as a promising therapeutic strategy for neurodegenerative diseases by targeting reversible gene expression changes without altering the underlying DNA sequence. This review explores key epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling, that contribute to neurodegeneration in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Pharmacological interventions such as DNA methylation modulators, histone deacetylase (HDAC) inhibitors, and non-coding RNA therapies have shown potential in restoring normal gene function. Advanced approaches, including CRISPR-dCas9 epigenetic editing, synthetic transcription factors (STFs), and Yamanaka factor-mediated cellular rejuvenation, offer precise control over disease-associated gene expression. Despite these advancements, several challenges and controversies remain, including off-target effects, delivery limitations, long-term safety concerns, and ethical implications. Emerging research focuses on multi-target combination therapies, integrating epigenetic interventions with stem cell therapy, immune checkpoint inhibitors, and AI-driven precision medicine. Future directions involve the development of non-invasive drug delivery systems, AI-powered biomarker discovery, and personalized epigenome-based treatments to enhance therapeutic outcomes. As research advances, epigenetic reprogramming holds the potential to revolutionize neurodegenerative disease treatment, providing more effective, individualized, and disease-modifying interventions.