GSK3‐ARC/Arg3.1 and GSK3‐Wnt signaling axes trigger amyloid‐β accumulation and neuroinflammation in middle‐aged Shugoshin 1 mice

Rao, Chinthalapally V.; Farooqui, Mudassir; Madhavaram, Avanish; Zhang, Yuting; Asch, Adam S.; Yamada, Hiroshi

doi:10.1111/acel.13221

Cited by 19 publications

(14 citation statements)

References 57 publications

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“…Wnt signaling pathways are critical in the pathogenesis of the AD (Vallée & Lecarpentier, 2016; Vallée et al, 2018). Wnt signaling pathway can regulate oxidative stress, inflammation, and apoptosis (Ali et al, 2020; Caricasole et al, 2004; Godoy et al, 2014; Rao et al, 2020; Sinha et al, 2015; Vallée et al, 2017; Yao et al, 2015; Yu et al, 2020). GSK‐3β is a dynamic and omnipresent serine/threonine‐protein kinase (Xu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK‐3β/β‐catenin signaling pathway

et al. 2022

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Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aβ1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5′-dithiobis (2-nitrobenzoic acid).Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubuleassociated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3β and βcatenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aβ1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3β, and β-catenin. In conclusion, by regulating the Wnt/GSK-3β/β-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons,

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK‐3β/β‐catenin signaling pathway

et al. 2022

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“…Example, recently it was shown that mutations of SGO2 (frameshift, p.Glu485Lysfs*5) and CLDN14 collectively cause coincidental Perrault syndrome which is a rare autosomal genetic disorder characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females [71,72]. Some of the studies in last few years also showed the involvement of shugoshin in neurological disorders like late-onset Alzheimer's disease (LOAD) [73,74]. It is important to mention that not all the diseased conditions are due to chromosome instability, which is induced by impaired shugoshin function of centromeric cohesion.…”

Section: Shugoshin In Other Clinical Disordersmentioning

confidence: 99%

Shugoshin: From a Perspective of Clinical Disorders

Kumar¹,

Agarwal²

2021

Preprint

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Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

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“…For example, recently it was shown that mutations of SGO2 (frameshift, p.Glu485Lysfs *5) and CLDN14 collectively cause coincidental Perrault syndrome, which is a rare autosomal genetic disorder characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females [71,72]. Some studies in the last few years also showed the involvement of shugoshin in neurological disorders such as late-onset Alzheimer's disease (LOAD) [73,74]. It is important to mention that not all the diseased conditions are due to chromosome instability, which is induced by impaired shugoshin function of centromeric cohesion.…”

Section: Shugoshin In Other Clinical Disordersmentioning

confidence: 99%

Shugoshin: From the Perspective of Clinical Disorders

Kumar

Agarwal

2021

BioChem

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Proper and timely segregation of the cellular genome is a prime requirement of all cell division programs. Mis-segregation of chromosomes and the resulting aneuploidy lead to several clinical consequences. Over the years, shugoshin has emerged as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or an altered level of shugoshin is reported in several human malignancies; as a result, shugoshin is now emerging as an important tumor-associated gene and a possible target for cancer therapy. Apart from its role in cancer, recent studies have also shown the involvement of shugoshin in several other clinical disorders. In this review, we aim to highlight the clinical relevance of shugoshin.

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GSK3‐ARC/Arg3.1 and GSK3‐Wnt signaling axes trigger amyloid‐β accumulation and neuroinflammation in middle‐aged Shugoshin 1 mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 57 publications

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK‐3β/β‐catenin signaling pathway

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK‐3β/β‐catenin signaling pathway

Shugoshin: From a Perspective of Clinical Disorders

Shugoshin: From the Perspective of Clinical Disorders

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