Dataset Information

Epigenetic resetting in the Parkinson's disease entail histone modification remodeling.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons (DN) in the substantia nigra and disrupted cellular maintenance. Here, we demonstrate that NDST3-mediated epigenetic reprogramming halts neuronal degeneration and restores motor function in a PD animal model. Following NDST3 administration, DN and associated circuits in the substantia nigra and striatum show marked revitalization, accompanied by significant alleviation of PD-like motor deficits. Integrative single-cell and spatial RNA sequencing with ChIP sequencing reveal that NDST3-driven reactivation of pathways linked to neuronal survival, synaptic integrity, steering compromised cells toward a resilient phenotype. By recalibrating the epigenetic landscape, NDST3 fosters cellular maintenance and functional recovery within key motor circuits. These findings highlight NDST3’s therapeutic potential as epigenetic modulator in PD. Our findings provide insights into the mechanisms underlying neuronal revitalization and underscore the promise of NDST3 as a novel agent for restoring brain function in neurodegenerative conditions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Neuronal Stem Cell

DISEASE(S): Parkinson's Disease

SUBMITTER: Yongwoo Na

LAB HEAD: Jong-Seo Kim

PROVIDER: PXD067971 | Pride | 2026-03-16

REPOSITORIES: Pride

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Publications

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

Chang Yujung Y Na Yongwoo Y Im Hyeonjoo H Yang Garam G Yang Seungseon S Shim Hyun Soo HS Kim Chunggoo C Kim GyeungYun G Park Hyeok Ju HJ Kim Hee Young HY Lee Seung Eun SE Lee Wonwoong W Ha Yoon Y Park Sungho S Kim Jieun J Cho Won-Young WY Sun Woong W Kim Jong-Seo JS Yoo Junsang J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20251121 14

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 ...[more]

PMID: 41268696

Similar Datasets

Project description:Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set?) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (?Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention. Analyzed samples include blood samples from 40 PD patients and 20 healthy controls. Of the original 60 samples, one (a control sample) did not pass the microarray hybridization quality controls and was excluded from further analyses. All results of bioinformatics analyses shown in this study refer to this set of 59 samples (reported here).

Project description:Background: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by both motor and non-motor symptoms, including olfactory dysfunction, which often precedes motor symptoms by several years. However, the underlying mechanisms linking olfactory dysfunction in PD to biological changes remain unclear. Recent studies suggest a potential connection between PD's olfactory dysfunction and alterations in the nasal microbiome and metabolome, but comprehensive investigations are still lacking.This study aims to explore the interplay between nasal microbiota, metabolites, and olfactory function in PD, identify potential biomarkers for early diagnosis, and investigate therapeutic targets for olfactory dysfunction in PD. Methods: From October 1, 2023, to September 30, 2024, 66 potential participants were enrolled, including PD patients with varying degrees of olfactory dysfunction and healthy controls. Nasal samples were collected for 16S rRNA sequencing and metabolomic analysis using GC-MS. The study also used MPTP-induced PD mouse models to assess the protective effects of cholic acid on olfactory function and dopaminergic neurons. Results: The study found significant differences in nasal microbiota composition and metabolite profiles between PD patients and controls, with correlations to the severity of olfactory dysfunction. Specifically, the relative abundances of Corynebacterium, Dolosigranulum, Muribacter, and Moraxella were elevated in the PD group, while the abundances of Hydrogenophaga, Staphylococcus, Klebsiella, and Bacillus decreased. Metabolomic analysis revealed that cholic acid, octanal, hexadecanol, and phytol were significantly altered in PD patients compared to controls, with cholic acid showing potential as a diagnostic biomarker (AUC > 0.97). In MPTP-induced PD mouse models, cholic acid treatment significantly reduced latencies in detecting buried food pellets, and increased tyrosine hydroxylase (TH)-positive fluorescence intensity in the olfactory bulb and substantia nigra. However, cholic acid did not significantly ameliorate motor symptoms in PD mice, as assessed by the open field test, and did not prevent the loss of TH+ cells in the striatum. Conclusion: The findings highlight the interplay between the nasal microbiome, metabolome, and olfactory dysfunction in PD, suggesting that modulating metabolic pathways could be a promising therapeutic strategy. Future research should focus on larger sample sizes, longitudinal studies, and further validation of biomarkers and therapeutic targets to enhance the understanding and management of PD.

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