ArticleNature communications2023
A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson's disease.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Calbindin stratifies midbrain dopaminergic neurons governing distinct aspects of locomotion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An atlas of primate insular cortex reveals a signal-processing strategy in von Economo neurons.Nature cell biology · 2026Article
- Integrating dorsolateral prefrontal cortex multi-omics and GWAS summary data reveals genetic etiology of Parkinson's disease.Research square · 2026Article
- Integrating dorsolateral prefrontal cortex multi-omics and GWAS summary data reveals genetic etiology of Parkinson's disease.medRxiv : the preprint server for health sciences · 2026Article
- Single-cell transcriptomics revealed molecular vulnerability in a human midbrain-like organoid model of Parkinson's disease.iScience · 2026Article
- Single-cell Multiome Analysis of Chromatin State and Transcriptome in the Human Basal Ganglia.bioRxiv : the preprint server for biology · 2026Article
- Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.Translational neurodegeneration · 2026Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Dysfunction of subthalamic dopaminergic circuitry contributes to anxiety- and depression-like behaviors in 6-OHDA lesion-induced hemiparkinsonian mice.Acta pharmacologica Sinica · 2025Article
- Understanding the Pre-Clinical Stages of Parkinson's Disease: Where Are We in Clinical and Research Settings?International journal of molecular sciences · 2025Review
- Gene delivery of SUMO1-derived peptide rescues neuronal degeneration and motor deficits in a mouse model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Single-cell RNA sequencing of adult primate neocortex reveals the regulatory dynamics of neural plasticity.American journal of translational research · 2025Article
- Review
- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2bioRxiv : the preprint server for biology · 2024Article
- An accelerated Parkinson's disease monkey model using AAV-α-synuclein plus poly(ADP-ribose).Cell reports methods · 2024Article
- Deficiency of parkin causes neurodegeneration and accumulation of pathological α-synuclein in monkey models.The Journal of clinical investigation · 2024Article
- Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson's disease model.NPJ Parkinson's disease · 2024Article
- Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP.Frontiers in aging neuroscience · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The degenerative process in Parkinson's disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls. Our primate model of parkinsonism recapitulates important pathologic features in nature PD and provides an unbiased view of the axis of neuronal vulnerability and resistance. We identified seven molecularly defined subtypes of nigral DaNs which manifested a gradient of vulnerability and were confirmed by fluorescence-activated nuclei sorting. Neuronal resilience was associated with a FOXP2-centered regulatory pathway shared between PD-resistant DaNs and glutamatergic excitatory neurons, as well as between humans and nonhuman primates. We also discovered activation of immune response common to glial cells of SN and PT, indicating concurrently activated pathways in the nigrostriatal system. Our study provides a unique resource to understand the mechanistic connections between neuronal susceptibility and PD pathophysiology, and to facilitate future biomarker discovery and targeted cell therapy.
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