Midbrain dopamine neurons in Parkinson׳s disease exhibit a dysregulated miRNA and target-gene network
Open accessAbstract
The degeneration of substantia nigra (SN) dopamine (DA) neurons in sporadic Parkinson׳s disease (PD) is characterized by disturbed gene expression networks. Micro(mi)RNAs are post-transcriptional regulators of gene expression and we recently provided evidence that these molecules may play a functional role in the pathogenesis of PD. Here, we document a comprehensive analysis of miRNAs in SN DA neurons and PD, including sex differences. Our data show that miRNAs are dysregulated in disease-affected neurons and differentially expressed between male and female samples with a trend of more up-regulated miRNAs in males and more down-regulated miRNAs in females. Unbiased Ingenuity Pathway Analysis (IPA) revealed a network of miRNA/target-gene associations that is consistent with dysfunctional gene and signaling pathways in PD pathology. Our study provides evidence for a general association of miRNAs with the cellular function and identity of SN DA neurons, and with deregulated gene expression networks and signaling pathways related to PD pathogenesis that may be sex-specific.
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miR-29 and five other miRNAs (miR-26, miR-30, miR-199b, miR-212, miR-380-5p) are upregulated in sporadic human PD brain.
“Out of the 81 miRNAs that inhibited PRKN translocation in our screen, miR-29 and five other miRNAs (miR-26 and miR-30, miR-199b, miR-212, miR-380-5p) have been reported to be upregulated in sporadic human PD brain [40–42].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [41]
Results §2.3 reports miR-26a among miRNAs upregulated in dopamine neurons from human PD patients, including the male subgroup. The available text does not report upregulation of miR-29, miR-30, miR-199b, miR-212, or miR-380-5p; searches for those names found no supporting passage. The source therefore supports only the miR-26 portion of the attributed list. (LLM, conf=0.86)
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MicroRNA Expression Profile Changes in the Leukocytes of Parkinson’s Disease Patients
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Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and menPreprint
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- Authors
- Briggs, C. E., Wang, Y., Kong, B., Woo, T.-U. W., Iyer, L. K., & Sonntag, K. C.
- Affiliations
- Tufts University (US)
- Harvard University (US)
- Corresponding author
- Sonntag, Kai C.
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 1618
- Pages
- 111-121
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4522231
- OpenAlex
- W583113781
- Cited by
- 113
- References
- 103
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 17 · 2022: 18 · 2021: 7 · 2020: 15 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 5 · 2015: 1
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts׳ Alzheimer׳s Disease Research Center
- Harvard NeuroDiscovery Center
- National Institute of Neurological Disorders and Stroke (R21NS067335)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, substantia nigra, dopaminergic neurons, microRNA, miRNA-target gene network, sex differences, neuronal gene expression, post-transcriptional regulation, signaling pathways, neuronal identity
- MeSH terms
- Female, Gene Expression Regulation, Humans, Male, Mesencephalon, Parkinson Disease, Signal Transduction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, Gene Regulatory Networks, Dopaminergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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