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Cited by 49Stress Responses and CortisolTreatment of Major DepressionTryptophan and brain disorders

The emerging role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in major depressive disorder: hypothesis and mechanisms

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Dattilo, Vincenzo, Amato, Rosario, Perrotti, Nicola, Gennarelli, Massimo·2020·Frontiers in Genetics
DOI 10.3389/fgene.2020.00826PMC PMC7419621
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Abstract

Major depressive disorder (MDD) is a heterogeneous psychiatric disease characterized by persistent low mood, diminished interests, and impaired cognitive and social functions. The multifactorial etiology of MDD is still largely unknown because of the complex genetic and environmental interactions involved. Therefore, no established mechanism can explain all the aspects of the disease. In this light, an extensive research about the pathophysiology of MDD has been carried out. Several pathogenic hypotheses, such as monoamines deficiency and neurobiological alterations in the stress-responsive system, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, have been proposed for MDD. Over time, remarkable studies, mainly on preclinical rodent models, linked the serum- and glucocorticoid-regulated kinase 1 (SGK1) to the main features of MDD. SGK1 is a serine/threonine kinase belonging to the AGK Kinase family. SGK1 is ubiquitously expressed, which plays a pivotal role in the hormonal regulation of several ion channels, carriers, pumps, and transcription factors or regulators. SGK1 expression is modulated by cell stress and hormones, including gluco- and mineralocorticoids. Compelling evidence suggests that increased SGK1 expression or function is related to the pathogenic stress hypothesis of major depression. Therefore, the first part of the present review highlights the putative role of SGK1 as a critical mediator in the dysregulation of the HPA axis, observed under chronic stress conditions, and its controversial role in the neuroinflammation as well. The second part depicts the negative regulation exerted by SGK1 in the expression of both the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), resulting in an anti-neurogenic activity. Finally, the review focuses on the antidepressant-like effects of anti-oxidative nutraceuticals in several preclinical model of depression, resulting from the restoration of the physiological expression and/or activity of SGK1, which leads to an increase in neurogenesis. In summary, the purpose of this review is a systematic analysis of literature depicting SGK1 as molecular junction of the complex mechanisms underlying the MDD in an effort to suggest the kinase as a potential biomarker and strategic target in modern molecular antidepressant therapy.

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Cited by

Sorted by citations

Authors
Dattilo, V., Amato, R., Perrotti, N., & Gennarelli, M.
Affiliations
  • Centro San Giovanni di Dio Fatebenefratelli (IT)
  • Magna Graecia University (IT)
Corresponding author
  • Dattilo, Vincenzo
  • Gennarelli, Massimo
ORCID
Venue
Frontiers in Genetics
Publisher
Frontiers Media SA
Published
2020-08-05
Volume
11
Pages
826-826
ISSN
1664-8021 (ISSN-L)
DOI
10.3389/fgene.2020.00826
PMC
PMC7419621
OpenAlex
W3047237128
Cited by
49
References
37
Citations by year
2026: 9 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 12 · 2021: 4
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
Ministero della Salute
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
SGK1, major depressive disorder, hypothalamic-pituitary-adrenal axis, chronic stress, neuroinflammation, brain-derived neurotrophic factor, vascular endothelial growth factor, neurogenesis, oxidative stress, nutraceuticals, antidepressant targets, biomarkers

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