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journal article·2026-03Open access

NDST3‐Induced Epigenetic Reprogramming Reverses Neurodegeneration in Parkinson's Disease

Yujung Chang, Yongwoo Na, Hyeonjoo Im, Garam Yang, Seungseon Yang, Hyun Soo Shim, Chunggoo Kim, GyeungYun Kim, Hyeok Ju Park, Hee Young Kim, Seung Eun Lee, Wonwoong Lee, Yoon Ha, Sungho Park, Jieun Kim, Won‐Young Cho, Woong Sun, Jong‐Seo Kim, Junsang Yoo

Advanced Science· Volume 13· Issue 14
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Source abstract

Abstract

Abstract 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.
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Research context

OpenAlex topics: Pluripotent Stem Cells Research · Nuclear Receptors and Signaling · Neurogenesis and neuroplasticity mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Laboratory of Regenerative Medicine for Neurodegenerative Disease Stand Up Therapeutics Inc. Hannamdaero 98 Seoul 04418 South Korea

Center for RNA Research Institute for Basic Science Seoul 08826 South Korea

School of Biological Sciences Seoul National University Seoul 08826 South Korea

Department of Anatomy College of Medicine Korea University Seoul 02841 South Korea

Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 South Korea

Biology Department Boston University Boston MA 02215 USA

Database Laboratory Department of Computer Science and Engineering Dongguk University Seoul 04620 South Korea

Department of Physiology College of Medicine Yonsei University Seoul 03722 South Korea

Research Animal Resource Center Korea Institute of Science and Technology Seoul 02792 South Korea

College of Pharmacy Woosuk University Wanju 55338 South Korea

Department of Neurosurgery College of Medicine Yonsei University Seoul 03722 South Korea

Department of Chemistry Yonsei University Seoul 03722 South Korea

Department of Bio‐Health Technology College of Biomedical Science and Multi‐dimensional Genomics Research Center Kangwon National University Chuncheon 24341 South Korea

Funding

Institute for Basic Science

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