Hippocampal overexpression of SGK1 ameliorates spatial memory, rescues Aβ pathology and actin cytoskeleton polymerization in middle-aged APP/PS1 mice
Abstract
The increasing occurrence and ineffective treatment of Alzheimer's disease (AD) has become one of the major challenges of the world. Limited studies have shown that serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in spatial memory formation and consolidation, but its role in AD-like spatial memory impairment and the related mechanisms are not clear. In this study, we first examined the age-related changes of SGK1 in the hippocampus of female APP/PS1 (AD) mice. Based on the finding and our previous finding that significant spatial memory impairment was detected in 8-month old AD mice, SGK1-overexpressing AAV (oSGK1) was constructed and injected into the hippocampus of 9-month old AD mice. One month later, the behavior alterations, Aβ production and deposit as well as changes of CA1 spine density and selected actin polymerization remodeling proteins were examined. The results showed that significant decrease of SGK1 was detected in 10-month old AD mice. The spatial memory impairment, the production and deposit of Aβ were reversed by oSGK1. Levels of hippocampal ADAM10 (α-secretase) and IDE (Aβ degradase), actin remodeling related proteins Rictor, Rac1, Cdc42 and Profilin-1 were significantly increased after oSGK1 treatment while hippocampal BACE1 (γ-secretase) and Cofilin remained unchanged. Taken together, our findings demonstrated a pivotal role of SGK1 in the treatment of AD-related memory impairment through upregulation of non- amyloidogenic processing of AP…
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In 10-month-old APP/PS1 mice, SGK1 expression is significantly reduced.
“In 10-month-old APP/PS1 mice, SGK1 expression is significantly reduced”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
Pathological states differ significantly across neurological diseases, and alterations in SGK1 vary, leading to distinct impacts of SGK1 on different diseases; even within the same disease, SGK1's influence on progression can vary.
“However, the pathological states differ significantly across various neurological diseases, and the alterations in SGK1 also vary, leading to distinct impacts of SGK1 on different diseases. Even within the same disease, the influence of SGK1 on its progression can vary”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
SGK1 plays a role in enhancing memory formation and reducing Aβ production, highlighting its potential in treatment of Alzheimer's disease.
“An increasing number of studies indicate that SGK1 plays a role in enhancing memory formation and reducing the production of Aβ, highlighting its potential in the treatment of AD”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
Overexpression of SGK1 reverses spatial memory impairments and decreases production and deposition of Aβ in APP/PS1 mice.
“When overexpressed, SGK1 reverses spatial memory impairments, as well as decrease the production and deposition of Aβ.”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
Upregulation of SGK1 elevates levels of actin remodeling-related proteins Rictor, Rac1, Cdc42, and Profilin-1 in the hippocampus of AD mice, which may impact neuronal structure and function.
“Furthermore, upregulation of SGK1 elevates the levels of actin remodeling-related proteins, such as Rictor, Rac1, Cdc42, and Profilin-1 in the hippocampus of AD mice, which may impact the structure and function of neurons”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
SGK1 maintains stable levels of BACE1 and Cofilin, indicating its influence does not involve promoting the amyloidogenic β pathway.
“Simultaneously, SGK1 maintains stable levels of BACE1 (β-secretase) and Cofilin, indicating its influence does not involve promoting the amyloidogenic β pathway”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
Increased SGK1 levels lead to a significant rise in hippocampal ADAM10 (α-secretase) and IDE (Aβ-degrading enzyme).
“The increased levels of SGK1 lead to a significant rise in hippocampal ADAM10 (α-secretase) and IDE (Aβ-degrading enzyme)”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Lian et al., 2020
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mTORC2 controls actin polymerization required for consolidation of long-term memory
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Significance of SGK1 in the regulation of neuronal function
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High-fat diet-induced activation of SGK1 promotes Alzheimer’s disease-associated tau pathology
Elahi, M., Motoi, Y., Shimonaka, S., Ishida, Y., Hioki, H., Takanashi, M., Ishiguro, K., Imai, Y., & Hattori, N. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab115 · Cited by 57 · see citing works
Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain
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Self-citation
- Authors
- Lian, B., Liu, M., Lan, Z., Sun, T., Meng, Z., Chang, Q., Liu, Z., Zhang, J., & Zhao, C.
- Affiliations
- Ningxia Medical University (CN)
- Army Medical University (CN)
- Corresponding author
- Zhang, Jiqiang
- Zhao, Chengjun
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 383
- Pages
- 112503
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W3002043570
- Cited by
- 19
- References
- 4
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chongqing Natural Science Foundation
- China Postdoctoral Science Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- SGK1, Alzheimer's disease, spatial memory, amyloid-beta, APP/PS1 mice, hippocampus, actin cytoskeleton, ADAM10, ide, Rictor, Rac1, Cdc42, profilin-1, synaptic plasticity, AAV gene overexpression, therapeutic target
- MeSH terms
- Morris Water Maze Test, Serum-Glucocorticoid Regulated Kinases, Animals, Behavior, Animal, Hippocampus, Humans, Immunohistochemistry, Mice, Transgenic, Actin Cytoskeleton, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Mice, Presenilin-1, Gene Knock-In Techniques, Spatial Memory
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