NDST3‐Induced Epigenetic Reprogramming Reverses Neurodegeneration in Parkinson's Disease
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.
Authors
- Yongwoo Na
- Shenjiao Yang
- Hyeonjoo Im
- Chunggoo Kim
- Yoon Soo Ha (ORCID: https://orcid.org/0000-0002-3775-2324)
- Woong Sun (ORCID: https://orcid.org/0000-0003-1792-4894)
- W. D. Cho
- Junsang Yoo (ORCID: https://orcid.org/0000-0002-9211-3963)
- Hyeok Ju Park
- Yu‐Jung Chang (ORCID: https://orcid.org/0000-0002-4781-0946)
- Gyeungyun Kim (ORCID: https://orcid.org/0000-0003-4382-503X)
- Jong‐Seo Kim (ORCID: https://orcid.org/0000-0002-8909-8440)
- Wonwoong Lee (ORCID: https://orcid.org/0000-0003-1455-5464)
- Sungho Park (ORCID: https://orcid.org/0000-0001-5435-3125)
- Ji‐Eun Kim (ORCID: https://orcid.org/0000-0002-3643-2177)
- Hee Young Kim (ORCID: https://orcid.org/0000-0002-2495-9115)
- Seung Eun Lee
- Guanghui Yang (ORCID: https://orcid.org/0000-0002-1390-8099)
- Hyun Soo Shim
Institutions
- Boston University (US)
- Seoul National University of Science and Technology (KR)
- Seoul National University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Kangwon National University (KR)
- Yonsei University (KR)
- Korea University (KR)
- Dongguk University (KR)
- Institute for Basic Science (KR)
- National Institute of Animal Science (KR)
- Io Therapeutics (United States) (US)
- Korea University (JP)
- Korea Institute of Science and Technology (KR)
- Woosuk University (KR)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1002/advs.202507323
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Institute for Basic Science
- Ministry of Science and ICT, South Korea