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

doi:10.1002/advs.202507323

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

Adv Sci (Weinh). 2026 Mar;13(14):e07323. doi: 10.1002/advs.202507323. Epub 2025 Nov 21.

Authors

Yujung Chang¹, Yongwoo Na^{2

3}, Hyeonjoo Im^{1

4}, Garam Yang^{1

5}, Seungseon Yang¹, Hyun Soo Shim¹, Chunggoo Kim¹, GyeungYun Kim⁶, Hyeok Ju Park⁷, Hee Young Kim⁸, Seung Eun Lee⁹, Wonwoong Lee¹⁰, Yoon Ha¹¹, Sungho Park¹², Jieun Kim¹³, Won-Young Cho¹⁰, Woong Sun⁴, Jong-Seo Kim^{2

3}, Junsang Yoo¹

Affiliations

¹ Laboratory of Regenerative Medicine for Neurodegenerative Disease, Stand Up Therapeutics Inc., Hannamdaero 98, Seoul, 04418, South Korea.
² Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.
³ School of Biological Sciences, Seoul National University, Seoul, 08826, South Korea.
⁴ Department of Anatomy, College of Medicine, Korea University, Seoul, 02841, South Korea.
⁵ Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea.
⁶ Biology Department, Boston University, Boston, MA, 02215, USA.
⁷ Database Laboratory, Department of Computer Science and Engineering, Dongguk University, Seoul, 04620, South Korea.
⁸ Department of Physiology, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
⁹ Research Animal Resource Center, Korea Institute of Science and Technology, Seoul, 02792, South Korea.
¹⁰ College of Pharmacy, Woosuk University, Wanju, 55338, South Korea.
¹¹ Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
¹² Department of Chemistry, Yonsei University, Seoul, 03722, South Korea.
¹³ Department of Bio-Health Technology, College of Biomedical Science and Multi-dimensional Genomics Research Center, Kangwon National University, Chuncheon, 24341, South Korea.

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.

Keywords: Parkinson's disease; cell vitalization; cellular repair; epigenetic reprogramming; neurodegenerative disease.

MeSH terms

Animals
Cellular Reprogramming / genetics
Disease Models, Animal
Dopaminergic Neurons / metabolism
Dopaminergic Neurons / pathology
Epigenesis, Genetic* / genetics
Humans
Male
Mice
Mice, Inbred C57BL
Parkinson Disease* / genetics
Parkinson Disease* / metabolism
Substantia Nigra / metabolism

Abstract

MeSH terms

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