Chang, Yujung Na, Yongwoo Im, Hyeonjoo Yang, Garam Yang, Seungseon Shim, Hyun Soo Kim, Chunggoo Kim, Gyeungyun Park, Hyeok Ju Kim, Hee Young Lee, Seung Eun Lee, Wonwoong Ha, Yoon Park, Sungho Kim, Jieun Cho, Won-Young Sun, Woong Kim, Jong-seo Yoo, Junsang 2025-12-19T07:02:18Z 2025-12-19T07:02:18Z 2025-12-19 2026-03 https://pubs.kist.re.kr/handle/201004/153811 Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons (DN) in the substantia nigra and disruption of cellular maintenance. Here, we demonstrate that NDST3-mediated epigenetic reprogramming halts neuronal degeneration and restores motor function in an animal model of PD. Following NDST3 administration, the DN and its associated circuits in the substantia nigra and striatum showed marked revitalization, accompanied by a considerable alleviation of PD-like motor deficits. Integrative single-cell and spatial RNA sequencing with CUT&RUN revealed that NDST3-driven reactivation of pathways is linked to neuronal survival, synaptic integrity, and steering of compromised cells toward a resilient phenotype. By recalibrating the epigenetic landscape, NDST3 promotes cellular maintenance and functional recovery in key motor circuits. These findings highlight NDST3's therapeutic potential as an epigenetic modulator of PD. These findings provide insights into the mechanisms underlying neuronal revitalization and highlight the potential of NDST3 as a novel agent for restoring brain function in neurodegenerative conditions. English Wiley-VCH Verlag NDST3-Induced Epigenetic Reprogramming Reverses Neurodegeneration in Parkinson's Disease Article 10.1002/advs.202507323 1 Advanced Science, v.13, no.14 Advanced Science 13 14 Y scie scopus 2-s2.0-105022619716 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article; Early Access EXTRACELLULAR RECORDINGS DOPAMINE TRANSPORTER IN-VIVO 6-OHDA NEURONS 6-HYDROXYDOPAMINE INHIBITION CORTEX CELLS BRAIN cell vitalization cellular repair epigenetic reprogramming neurodegenerative disease Parkinson&apos s disease