Elevated β-secretase 1 expression mediates CD4+ T cell dysfunction via PGE2 signalling in Alzheimer’s disease

Dai, Linbin; Wang, Qiong; Lv, Xinyi; Chen, Zuolong; Shen, Yong

doi:10.1016/j.bbi.2021.08.234

Cited by 8 publications

(6 citation statements)

References 56 publications

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“…Surprisingly, recent studies identified that CD4+ T cells highly expressed BACE1, and BACE1 mediated T-cell activation in the EAE and AD mouse model (Dai et al, 2021;Hernandez-Mir et al, 2019).…”

Section: T-cell Function Is Associated With β-Secretasementioning

confidence: 99%

Insights into T‐cell dysfunction in Alzheimer's disease

Dai

Shen

2021

Aging Cell

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Section: T-cell Function Is Associated With β-Secretasementioning

confidence: 99%

Insights into T‐cell dysfunction in Alzheimer's disease

Dai

Shen

2021

Aging Cell

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“…There is much evidence in the literature that oxidative stress and inflammatory responses are both key factors for the pathogenesis of neurodegeneration [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Alzheimer’s disease is the most common neurodegenerative disorder, characterized by memory loss and cognitive impairment.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Prostaglandins, formed by arachidonic acid cleavage mediated by Cyclooxygenase (COX), are considered key factors in AD development [ 13 ]. Especially PGE2 has been found to inhibit phagocytosis of β-amyloid peptides and enhances neurotoxic activity of microglia [ 14 ]. Moreover, both amyloid plaques and NFT formation are highly associated with lipoxygenase (LOX) activity, which has been found to increase with age [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

2022

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Alzheimer’s Disease (AD) is a common neurodegenerative disorder characterized by memory loss and cognitive impairment. Its pathology has not been fully clarified and therefore highly effective treatments have not been obtained yet. Almost all the current treatment options aim to alleviate only the symptoms and not to eliminate the disease itself. Acetylcholinesterase inhibitors are the main therapeutic agents against AD, whereas oxidative stress and inflammation have been found to be of great significance for the development and progression of neurodegeneration. In this work, ethyl nipecotate (ethyl-piperidine-3-carboxylate), a heterocyclic carboxylic acid derivative, which acts as a GABA reuptake inhibitor and has been used in research for diseases involving GABAergic neurotransmission dysfunction, was amidated with various carboxylic acids bearing antioxidant and/or anti-inflammatory properties (e.g., ferulic acid, sinapic acid, butylated hydroxycinnamic acid). Most of our compounds have significant antioxidant potency as lipid peroxidation inhibitors (IC50 as low as 20 μΜ), as oxidative protein glycation inhibitors (inhibition up to 57%), and act as DPPH reducing agents. Moreover, our compounds are moderate LOX inhibitors (up to 33% at 100 μΜ) and could reduce rat paw edema induced by carrageenan by up to 61%. Finally, some of them possessed inhibitory activity against acetylcholinesterase (IC50 as low as to 47 μΜ). Our results indicate that our compounds could have the potentiality for further optimization as multi-targeting agents directed against AD.

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“…Furthermore, there are currently no good methods or drugs to help patients with AD to recover or gain an improved quality of life, and the exact mechanism of AD remains elusive. From a data perspective, recent studies have focused on exploring effective targets for AD ( Chong et al, 2021 ); some genes, including oncogenes and suppressor genes, have been found, such as β-secretase 1 ( BACE1 ) ( Dai et al, 2021 ) and receptor-interacting protein kinase 1 ( RIPK1 ) ( Li et al, 2021 ). Nevertheless, novel biomarkers with high sensitivity, specificity, and efficiency are necessary to improve AD diagnosis, understand immune infiltration, and treat this disease.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis and identification of hub genes as novel biomarkers for Alzheimer’s disease

Zhao

Zhang²,

Wu³

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is an intractable and progressive neurodegenerative disorder that can lead to severe cognitive decline, impaired speech, short-term memory loss, and finally an inability to function in daily life. For patients, their families, and even all of society, AD can impart great emotional pressure and economic costs. Therefore, this study aimed to investigate potential diagnostic biomarkers of AD. Using the Gene Expression Omnibus (GEO) database, the expression profiles of genes were extracted from the GSE5281, GSE28146, and GSE48350 microarray datasets. Then, immune-related genes were identified by the intersections of differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA), were performed. Subsequently, random forest models and least absolute shrinkage and selection operator regression were used to further screen hub genes, which were then validated using receiver operating characteristic (ROC) curve analysis. Finally, 153 total immune-related DEGs were identified in relation to AD. DO analysis of these immune-related DEGs showed that they were enriched in “lung disease,” “reproductive system disease,” and “atherosclerosis.” Single GSEA of hub genes showed that they were particularly enriched in “oxidative phosphorylation.” ROC analysis of AGAP3 yielded an area under the ROC curve of 0.878 for GSE5281, 0.727 for GSE28146, and 0.635 for GSE48350. Moreover, immune infiltration analysis demonstrated that AGAP3 was related to follicular helper T cells, naïve CD4 T cells, naïve B cells, memory B cells, macrophages M0, macrophages M1, macrophages M2, resting natural killer (NK) cells, activated NK cells, monocytes, neutrophils, eosinophils, and activated mast cells. These results indicate that identifying immune-related DEGs might enhance the current understanding of the development and prognosis of AD. Furthermore, AGAP3 not only plays a vital role in AD progression and diagnosis but could also serve as a valuable target for further research on AD.

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Elevated β-secretase 1 expression mediates CD4+ T cell dysfunction via PGE2 signalling in Alzheimer’s disease

Cited by 8 publications

References 56 publications

Insights into T‐cell dysfunction in Alzheimer's disease

Insights into T‐cell dysfunction in Alzheimer's disease

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study

Integrated analysis and identification of hub genes as novel biomarkers for Alzheimer’s disease

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