ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Brain-Wide Neuroregenerative Gene Therapy Improves Cognition in a Mouse Model of Alzheimer's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Therapeutic potential of astrocyte transdifferentiated neurons.Neural regeneration research · 2026Article
- Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.International journal of molecular sciences · 2026Article
- Overexpressing neurogenic differentiation factor 1 in Müller cells improves retinal function after optic nerve crush injury in adult mice.Neural regeneration research · 2026Article
- NeuroD1 gene therapy inhibits glioma growth and extends life span throughMolecular therapy. Oncology · 2026Article
- Recent advances in self-assembled nanoplatforms for central nervous system disorders therapy: Design principles, multifunctional strategies, and therapeutic applications.Materials today. Bio · 2026Review
- A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair in Alzheimer's Disease-Like Non-Human Primate Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A single-cell transcriptomic dataset profiling traumatic brain injury and NeuroD1-based gene therapy in mice.Scientific data · 2026Article
- Olig2 acts as an inducible barrier to in vivo astrocyte-to-neuron conversion.Nature communications · 2026Article
- Ferroptosis-related biomarkers for diagnosis and mechanistic insights into Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- Dynamic regulation of NeuroD1 expression level by a novel viral construct during astrocyte-to-neuron reprogramming.Molecular therapy. Nucleic acids · 2025Article
- Nanoplatform-Enabled Genetic Interventions for Central Nervous System Disorders: Advances in Delivery Strategies and Therapeutic Potential.Advanced genetics (Hoboken, N.J.) · 2025Review
- Brain-Wide Neuroregenerative Gene Therapy Improves Cognition in a Mouse Model of Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Alzheimer's disease (AD) is a progressive and irreversible brain disorder with extensive neuronal loss in the neocortex and hippocampus. Current therapeutic interventions focus on the early stage of AD but lack effective treatment for the late stage of AD, largely due to the inability to replenish the lost neurons and repair the broken neural circuits. In this study, by using engineered adeno-associated virus vectors that efficiently cross the blood-brain-barrier in the mouse brain, a brain-wide neuroregenerative gene therapy is developed to directly convert endogenous astrocytes into functional neurons in a mouse model of AD. It is found that ≈500 000 new neurons are regenerated and widely distributed in the cerebral cortex and hippocampus. Importantly, it is demonstrated that the converted neurons can integrate into pre-existing neural networks and improve various cognitive performances in AD mice. Chemogenetic inhibition of the converted neurons abolishes memory enhancement in AD mice, suggesting a pivotal role for the newly converted neurons in cognitive restoration. Together, brain-wide neuroregenerative gene therapy may provide a viable strategy for the treatment of AD and other brain disorders associated with massive neuronal loss.
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Registered trials
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