A Beacon of Hope: Paving the Path to Neural Recovery

Neuroscience continues to face a central challenge with profound clinical consequences: neuronal loss and network dysfunction in chronic neurodegenerative disease and after acute brain injury. Neuronal death, impaired replacement, and failed circuit rewiring disrupt information flow across brain networks, manifesting as progressive cognitive and motor decline in disorders such as Alzheimer’s and Parkinson’s diseases, or as sudden and often severe deficits following ischemic stroke, traumatic brain injury or spinal cord lesions. While extensive work has identified molecular contributors to degeneration—including excitotoxicity, mitochondrial dysfunction, oxidative stress, proteostasis impairment, neuroinflammation, and regulated cell-death pathways—translation into disease-modifying therapies remains limited. This gap reflects the complexity of CNS repair, where outcomes depend on tightly coupled interactions among neurons, glia, immune cells, and the neurovascular unit, as well as on the timing, specificity, and durability of therapeutic modulation.Recent advances have renewed optimism by revealing endogenous repair programs and experimentally tractable molecular “switches” that can enable regeneration and circuit remodeling in the adult brain. Progress in adult neurogenesis, axon and dendrite growth, synaptogenesis, remyelination, and extracellular matrix remodeling suggests that repair is constrained by integrated inhibitory cues and cell-state barriers rather than by a single pathway. Emerging strategies—spanning gene and RNA-based modulation, small-molecule interventions, targeted delivery approaches, and cell-based therapies—are beginning to define how regenerative trajectories can be initiated, shaped, and stabilized. A key next step is to map repair at cell-type resolution and connect molecular mechanisms to functional outcomes, using modern multi-omics, perturbation methods, and circuit-level assays.This Research Topic aims to accelerate mechanistic and translational progress by inviting studies that deepen our understanding of neuronal regeneration and network reconstruction across disease and injury contexts. We welcome contributions that dissect molecular and cellular programs governing neuronal survival, neurogenesis and fate specification, neurite outgrowth, synaptic remodeling, myelination, and immune–glial regulation, and that evaluate therapeutic approaches capable of engaging these pathways in vivo. By integrating molecular mechanisms with rigorous functional validation and translational feasibility, this Research Topic seeks to advance a roadmap for durable neural repair.We welcome articles addressing, but not limited to, the following themes:• Molecular regulation of adult neurogenesis, lineage progression, and fate specification (including single-cell and spatial approaches)• Neuron–glia–immune signaling in degeneration versus repair (astrocytes, microglia, oligodendrocyte lineage cells; neurovascular unit)• Epigenetic, transcriptional, and metabolic control of regenerative competence and cell-state transitions• Proteostasis, mitochondrial pathways, and regulated cell-death mechanisms as targets for neuroprotection and regeneration• Therapeutic modalities for neural repair: gene/RNA therapies, CRISPR-based perturbation and screening, and pharmacological interventions• Stem cell and transplantation strategies: integration, maturation, remyelination, and safety• Extracellular matrix remodeling, axon guidance, synaptogenesis, and connectivity restoration• Translational challenges: delivery, target engagement, biomarkers, durability of effect, and adverse outcomes Topic editors: Susana Solá, Tiago F Outeiro, Ilaria Decimo Source: https://www.frontiersin.org/research-topics/79495/a-beacon-of-hope-paving-the-path-to-neural-recovery