Evidence map›Paper›PMID 39267160›Full record

ArticleStem cell research & therapy2024

DVL/GSK3/ISL1 pathway signaling: unraveling the mechanism of SIRT3 in neurogenesis and AD therapy.

Nan Dai, Xiaorong Su, Aihua Li, Jinglan Li, Deqi Jiang, Yong Wang

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Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Nan Dai *Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Xiaorong Su *Department of Pharmacy, Women and Children's Hospital, School of Medicine, Xiamen University, 10# Zhenhai Road, Xiamen, China.
Aihua LiDepartment of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Jinglan LiDepartment of Pharmacy, Shenzhen Second People's Hospital, Shenzhen, 518000, China.
Deqi JiangDepartment of Biology and Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China.
Yong WangDepartment of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China. wy43555@smu.edu.cn.ORCID 0000-0001-9371-8991

Funding

Guangdong Yiyang Healthcare Charity Foundation JZ2022010the Natural Science Foundation of Guangdong Province 2020A1515010230
6 · The paper itself

Abstract

backgroundThe established association between Alzheimer's disease (AD) and compromised neural regeneration is well-documented. In addition to the mitigation of apoptosis in neural stem cells (NSCs), the induction of neurogenesis has been proposed as a promising therapeutic strategy for AD. Our previous research has demonstrated the effective inhibition of NSC injury induced by microglial activation through the repression of oxidative stress and mitochondrial dysfunction by Sirtuin 3 (SIRT3). Nonetheless, the precise role of SIRT3 in neurogenesis remains incompletely understood.

methodsIn vivo, SIRT3 overexpression adenovirus was firstly injected by brain stereotaxic localization to affect the hippocampal SIRT3 expression in APP/PS1 mice, and then behavioral experiments were performed to investigate the cognitive improvement of SIRT3 in APP/PS1 mice, as well as neurogenic changes in hippocampal region by immunohistochemistry and immunofluorescence. In vitro, under the transwell co-culture condition of microglia and neural stem cells, the mechanism of SIRT3 improving neurogenesis of neural stem cells through DVL/GSK3/ISL1 axis was investigated by immunoblotting, immunofluorescence and other experimental methods.

resultsOur findings indicate that the overexpression of SIRT3 in APP/PS1 mice led to enhanced cognitive function and increased neurogenesis. Additionally, SIRT3 was observed to promote the differentiation of NSCs into neurons during retinoic acid (RA)-induced NSC differentiation in vitro, suggesting a potential role in neurogenesis. Furthermore, we observed the activation of the Wnt/ß-catenin signaling pathway during this process, with Glycogen Synthase Kinase-3a (GSK3a) primarily governing NSC proliferation and GSK3ß predominantly regulating NSC differentiation. Moreover, the outcomes of our study demonstrate that SIRT3 exerts a protective effect against microglia-induced apoptosis in neural stem cells through its interaction with DVLs.

conclusionsOur results show that SIRT3 overexpressing APP/PS1 mice have improved cognition and neurogenesis, as well as improved neurogenesis of NSC in microglia and NSC transwell co-culture conditions through the DVL/GSK3/ISL1 axis.

Indexed as

Alzheimer DiseaseNeural Stem CellsNeurogenesisSignal TransductionSirtuin 3AnimalsCell DifferentiationDishevelled ProteinsGlycogen Synthase Kinase 3HippocampusMiceMice, TransgenicMicrogliaDishevelled ProteinsGlycogen Synthase Kinase 3Sirt3 protein, mouseSirtuin 3Neural stem cellsNeurogenesisNeuronal differentiationSIRT3Wnt/β-catenin pathway

Identifiers

PMID39267160
PMCPMC11395226

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