Astrocyte-to-Neuron Reprogramming via Neurogenin2: A Dual Strategy for Circuit Restoration and Antioxidant Defense in Congenital Blindness and Deafness

Background: Congenital blindness and deafness are major causes of lifelong disability, characterized by irreversible sensory circuit loss. Current therapies remain limited, particularly because neurons are highly vulnerable to oxidative stress, which exacerbates neurodegeneration and impairs circuit repair. Astrocytes, traditionally regarded as supportive cells, have emerged as crucial regulators of antioxidant homeostasis through pathways such as Nrf2/ARE, glutathione metabolism, and reactive oxygen species (ROS) scavenging. Objective: This review explores the potential of astrocyte-to-neuron reprogramming via the proneural transcription factor Neurogenin2 (Ngn2) as a dual therapeutic strategy for restoring lost neuronal circuits and enhancing antioxidant defenses in congenital sensory deficits. Methods: A systematic literature review was conducted across databases including PubMed, ClinicalKey, Elsevier, NCBI, and Scielo (2010–2021). Approximately 120 articles were screened and analyzed based on relevance to neuronal reprogramming, oxidative stress, and astrocytic plasticity, with particular emphasis on molecular pathways linking redox balance and neuronal fate specification. Results: Astrocytes share genetic signatures with neurons and possess intrinsic antioxidant capacities, positioning them as optimal candidates for reprogramming. Ngn2-mediated reprogramming increases astrocyte-to-neuron conversion efficiency from 4% to 13.4%. Furthermore, astrocytes actively regulate ROS metabolism and maintain glutathione pools, suggesting that newly generated neurons may inherit or be engineered to retain antioxidant properties. Conclusion: Ngn2-driven astrocyte reprogramming represents a promising therapeutic avenue not only for reconstructing lost neuronal circuits in congenital blindness and deafness but also for reinforcing redox balance. The integration of neuroregeneration and antioxidant defense opens a novel perspective in translational neuroscience.