Neurodegeneration in Alzheimer’s disease outpaces the brain’s ability to regenerate neurons. Wang et al. develop a Nano-ERASER platform that delivers anti-PTBP1 antibodies into astrocytes, enabling proteasome-mediated PTBP1 degradation and activating neuronal reprogramming. This nanotechnology-based Trim-Away system induces functional neurogenesis in vitro, in human brain organoids, and in AD mouse brains, thereby improving learning and memory. The study introduces a regenerative therapeutic paradigm in which biomaterials and endogenous glia collaborate to rebuild neural circuits in Alzheimer’s disease.