Direct neuronal reprogramming: emerging therapeutic strategies for neurodegenerative disorders

BACKGROUND: strategies that address older problems, and analyse clinical trial outcomes to identify key knowledge gaps to guide future research. DISCUSSION: approaches have emerged. These techniques employ small molecules, nonviral gene delivery, and CRISPR-based activation to reduce protocol complexity and improve cell survival. Combined methodologies integrate transcription factor cocktails with epigenetic modifiers, microRNAs, and neurotrophic factors, and show further enhancements. Despite these advances, translation to clinical applications has been modest. Early-phase trials report limited functional improvements and highlight risks of off-target effects, inconsistent delivery specificity, and unresolved immunogenicity. CONCLUSIONS: and combined approaches show promise in addressing the shortcomings of traditional methods. However, further preclinical validation, comprehensive safety assessments, and uniform frameworks are essential for clinical translation. Future studies should prioritize refining delivery platforms, minimizing off-target reprogramming events, and developing robust biomarkers to monitor conversion efficiency and functional outcomes.