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Cited by 18Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Decreased expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes alpha-synuclein increase related with down-regulation of dopaminergic cell in the substantia Nigra of chronic MPTP-induced parkinsonism mice and in SH-SY5Y cells

Yeo, Sujung, Sung, Backil, Hong, Yeon-Mi, van den Noort, Maurits, Bosch, Peggy, Lee, Sook-Hyun, Song, Jongbeom, Park, Sang-Kyun +1 more·2018·Gene
DOI 10.1016/j.gene.2018.03.086
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Abstract

Parkinson's disease (PD) is a chronically progressive neurodegenerative disease, with its main pathological hallmarks being a dramatic loss of dopaminergic neurons predominantly in the Substantia Nigra (SN), and the formations of intracytoplasmic Lewy bodies and dystrophic neurites. Alpha-synuclein (α-syn), widely recognized as the most prominent element of the Lewy body, is one of the representative hallmarks in PD. However, the mechanisms behind the increased α-syn expression and aggregation have not yet been clarified. To examine what causes α-syn expression to increase, we analyzed the pattern of gene expression in the SN of mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where down-regulation of dopaminergic cells occurred. We identified serum- and glucocorticoid-dependent kinase 1 (SGK1) as one of the genes that is evidently downregulated in chronic MPTP-intoxication. The results of Western blot analyses showed that, together with the down-regulation of dopaminergic cells, the decrease in SGK1 expression increased α-syn expression in the SN in a chronic MPTP-induced Parkinsonism mouse. For an examination of the expression correlation between SGK1 and α-syn, SH-5YSY cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of α-syn were observed. These results suggest that decreased expression of SGK1 may play a critical role in increasing the expression of α-syn, which is related with dopaminergic cell death in the SN of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.

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Cited by

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Authors
Yeo, S., Sung, B., Hong, Y.-M., van den Noort, M., Bosch, P., Lee, S.-H., Song, J., Park, S.-K., & Lim, S.
Affiliations
  • Sangji University (KR)
  • Pacific Union College (US)
  • Kyung Hee University (KR)
  • Radboud University Nijmegen (NL)
Corresponding author
  • Yeo, Sujung
  • Lim, Sabina
ORCID
Venue
Gene
Publisher
Elsevier BV
Published
2018-06
Volume
661
Pages
189-195
ISSN
0378-1119 (ISSN-L)
DOI
10.1016/j.gene.2018.03.086
OpenAlex
W2794702549
Cited by
18
References
2
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2021: 6 · 2019: 2
FWCI
1.37
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gene (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
Ministry of Science, ICT and Future Planning (2017R1D1A3B03030933)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
SGK1, serum- and glucocorticoid-inducible kinase 1, alpha-synuclein, Parkinson's disease, substantia nigra, dopaminergic neuron loss, MPTP-induced parkinsonism, Lewy bodies, gene downregulation, SH-SY5Y cells, siRNA knockdown
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Cell Count, Cell Line, Chronic Disease, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Parkinson Disease, Secondary, Substantia Nigra, Down-Regulation, Protein Serine-Threonine Kinases, Immediate-Early Proteins, MPTP Poisoning, Mice, alpha-Synuclein, Dopaminergic Neurons

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