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Cited by 121Parkinson's Disease Mechanisms and TreatmentsBioinformatics and Genomic NetworksNuclear Receptors and Signaling

The landscape of multiscale transcriptomic networks and key regulators in Parkinson’s disease

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Wang, Qian, Zhang, Yuanxi, Wang, Minghui, Song, Won-Min, Shen, Qi, McKenzie, Andrew, Choi, Insup, Zhou, Xianxiao +3 more·2019·Nature Communications
DOI 10.1038/s41467-019-13144-yPMC PMC6868244
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Abstract

Genetic and genomic studies have advanced our knowledge of inherited Parkinson’s disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes. Our network analysis predicts a function of human STMN2 in synaptic trafficking, which is validated in Stmn2-knockdown mouse dopaminergic neurons. Stmn2 reduction in the mouse midbrain causes dopaminergic neuron degeneration, phosphorylated α-synuclein elevation, and locomotor deficits. Our integrative analysis not only begins to elucidate the global landscape of PD transcriptomic networks but also pinpoints potential key regulators of PD pathogenic pathways.

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Cited by

Sorted by citations

Authors
Wang, Q., Zhang, Y., Wang, M., Song, W.-M., Shen, Q., McKenzie, A., Choi, I., Zhou, X., Pan, P.-Y., Yue, Z., & Zhang, B.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
  • Yue, Zhenyu
  • Zhang, Bin
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-20
Volume
10
Issue
1
Pages
5234-5234
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13144-y
PMC
PMC6868244
OpenAlex
W2989971001
Cited by
121
References
12
Citations by year
2026: 6 · 2025: 8 · 2024: 31 · 2023: 12 · 2022: 27 · 2021: 21 · 2020: 15 · 2019: 1
FWCI
2.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health & Human Services | National Institutes of Health (P50NS094733, R01NS060809, U01AG046170, RF1AG057440)
  • Mount Sinai Seed Funds
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, transcriptomic networks, gene regulatory networks, substantia nigra, STMN2, stathmin, dopaminergic neurons, alpha-synuclein phosphorylation, locomotor deficits, mouse model, idiopathic Parkinson's disease
MeSH terms
Animals, Humans, Locomotion, Parkinson Disease, Phosphorylation, Substantia Nigra, Gene Expression Profiling, Stathmin, Mice, alpha-Synuclein, Gene Regulatory Networks, Gene Knockdown Techniques, Dopaminergic Neurons, Transcriptome

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