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Cited by 12Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingGastrointestinal motility and disorders

Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson’s Disease

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Seo, Min Hyung, Kwon, Dasom, Kim, Soo-Hwan, Yeo, Sujung·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms242216408PMC PMC10671719
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Abstract

Parkinson’s disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased α-synuclein (α-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the association between serum/glucocorticoid-related kinase 1 (SGK1) and α-syn in the colon of a PD mouse model. SGK1 and α-syn expression patterns were opposite in the surrounding colon tissue, with decreased SGK1 expression and increased α-syn expression in the PD group. Immunofluorescence analyses revealed the colocation of SGK1 and α-syn; the PD group demonstrated weaker SGK1 expression and stronger α-syn expression than the control group. Immunoblotting analysis showed that Na+/K+ pump ATPase α1 expression levels were significantly increased in the PD group. In SW480 cells with SGK1 knockdown using SGK1 siRNA, decreasing SGK1 levels corresponded with significant increases in the expression levels of α-syn and ATPase α1. These results suggest that SGK1 significantly regulates Na+/K+ pump ATPase, influencing the relationship between electrolyte balance and fecal formation in the PD mouse model. Gastrointestinal disorders are some of the major prodromal symptoms of PD. Therefore, modulating SGK1 expression could be an important strategy for controlling PD.

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  • Downregulation of SGK1 can exacerbate progression of Parkinson's disease through various mechanisms.

    “Multiple studies have shown that the downregulation of SGK1 can exacerbate the progression of PD through various mechanisms”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Seo et al., 2023

    The Discussion links reduced SGK1 to several possible PD-related mechanisms, including loss of neuroprotection and increased intestinal α-synuclein. It says reduced SGK1 may imply accelerated deterioration, but does not demonstrate that downregulation exacerbates PD progression; it also reports that SGK1 inhibition in glia improved outcomes in an animal model. Page numbers were not provided in our copy. (LLM, conf=0.83)

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  • In peripheral colonic tissues of PD groups, SGK1 expression is notably decreased alongside increased α-syn expression; suppressing SGK1 expression exacerbates expression of genes associated with PD-related constipation.

    “In the peripheral colonic tissues of PD groups, there is a notable decrease in the expression of SGK1, alongside an increase in α-syn expression. Additionally, suppressing SGK1 expression exacerbates the expression of genes associated with PD-related constipation”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Seo et al., 2023

    The Discussion (§3) reports decreased SGK1 and increased α-syn in the colon of MPTP-induced PD mice. Results (§2.4) report that SGK1 knockdown in SW480 cells increased α-syn and Na+/K+ pump ATPase α1 expression, but the paper presents their connection to constipation as an inference, not a demonstrated exacerbation of constipation-related gene expression. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Seo, M. H., Kwon, D., Kim, S.-H., & Yeo, S.
Affiliations
  • Sangji University (KR)
  • Yonsei University (KR)
Corresponding author
  • Kim, Soo-Hwan
  • Yeo, Sujung
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-11-16
Volume
24
Issue
22
Pages
16408
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms242216408
PMC
PMC10671719
OpenAlex
W4388733769
Cited by
12
References
5
Citations by year
2026: 5 · 2025: 3 · 2024: 4
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation of Korea (NRF) (2020R1I1A3A04036500, HF20C0019)
  • Korea Health Technology R&D Project (2020R1I1A3A04036500, HF20C0019)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
Parkinson's disease, SGK1, alpha-synuclein, MPTP mouse model, gastrointestinal symptoms, dopaminergic neuron loss, SW480 cells, electrolyte balance
MeSH terms
Adenosine Triphosphatases, Animals, Disease Models, Animal, Gastrointestinal Diseases, Glucocorticoids, Parkinson Disease, Neurodegenerative Diseases, Mice, alpha-Synuclein, Dopaminergic Neurons

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