The Role of Natural Killer Cells in Alzheimer’s Disease

Jadidi‐Niaragh, Farhad; Shegarfi, Hamid; Naddafi, Fatemeh; Mirshafiey, Abbas

doi:10.1111/j.1365-3083.2012.02769.x

Cited by 36 publications

(28 citation statements)

References 64 publications

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“…It is shared in the GWAS and expression datasets. Natural killer cells play an important role in host defence, and are involved in AD immunopathogenesis [26]. The increased natural killer cell cytotoxicity in AD may involve protein kinase C dysregulation [27].…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

et al. 2016

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In recent years, several pathway analyses of genome-wide association studies reported the involvement of metabolic and immune pathways in Alzheimer's disease (AD). Until now, the exact mechanisms of these pathways in AD are still unclear. Here, we conducted a pathway analysis of a whole genome AD case-control expression dataset (n=41, 25 AD cases and 16 controls) from the human temporal cortex tissue. Using the differently expressed AD genes, we identified significant KEGG pathways related to metabolism and immune processes. Using the up- and down- regulated AD gene list, we further found up-regulated AD gene were significantly enriched in immune and metabolic pathways. We further compare the immune and metabolic KEGG pathways from the expression dataset with those from previous GWAS datasets, and found that most of these pathways are shared in both GWAS and expression datasets.

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

et al. 2016

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“…NK cells are an important part of the host defense and the immune system has been suggested as severely disturbed in AD [29,30]. Furthermore, NK cells have been proposed as involved in the pathogenesis of AD in studies performed in humans and animal models [31][32][33][34][35][36][37][38][39]. However, the role of NK cells in AD has not been sufficiently explored, especially when the accumulation of postzygotic mutations acquired during lifetime (such as LOY) is considered.…”

Section: Introductionmentioning

confidence: 99%

Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes

Dumanski

Halvardson

Davies

et al. 2019

Preprint

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Mosaic loss of chromosome Y (LOY) in blood is linked to increased risk for morbidity and mortality in men. LOY is the most common acquired mutation and is associated with diseases such as cancer and Alzhemer's disease. We studied DNA, RNA and proteins in bulk, sorted-and single-cells in vivo and in vitro. We show that Alzheimer's disease and prostate cancer patients had more LOY in NK cells and CD4+ T-lymphocytes, respectively. Furthermore, gene expression was profoundly altered in cells with LOY in a pleiotropic fashion and autosomal genes important for normal immune cell functions showed LOY associated transcriptional effect. Proteomic analysis also indicated that LOY leaves a footprint in the plasma proteome. We provide the first mechanistic explanation for the associations between LOY in blood and risk for disease in other organs.Recent epidemiological analyses have challenged the view that LOY in blood cells is phenotypically neutral. Studies have identified increased risks for men with LOY in connection with all-cause mortality [8,9], Alzheimer's disease [10], various forms of cancer [8,[11][12][13], autoimmune conditions [14,15], age-related macular degeneration [16], cardiovascular disease [17], type 2 diabetes and obesity [9]. Furthermore, it has been known for centuries that males have a shorter life expectancy [18][19][20]. Hence, LOY as a male specific risk factor, showing reproducible associations with various common disorders, could help explaining this difference.LOY in blood is the most frequent post-zygotic mutation, detectable in 20% of the UK Biobank male population [21], reaching 40% in 80 years old males [22], and 57% in 93 years old males [23]. Furthermore, LOY is not restricted to the hematopoietic system, since it has also been described in other non-cancerous tissues, although with much lower frequencies [17,23]. Our understanding of why LOY occurs is also limited. Strong associations with age and smoking have been reported [8,10,24,25] and these factors are related to a continuously increasing mutational load throughout the genome in all somatic cells, eventually also affecting genes that are responsible for correct segregation of chromosomes. Inherited genetic predisposition for LOY has also been described [21,25,26].It is not known whether associations between LOY and increased risks for disease represent causal relationships, and if so, what the underlying mechanisms could be. The challenge that we address here is to move from epidemiological associations to mechanistic explanations on multiple levels of analysis such as DNA, mRNA and proteins. Specifically, we studied: (i) frequency of LOY in subsets of leukocytes from patients with prostate cancer (PC), Alzheimer's disease (AD) as well as controls; (ii) changes in transcriptomes of single cells and cellular subsets in bulk; and (iii) alterations of plasma protein levels in men with LOY. Different distribution of LOY in six types of sorted leukocytes among men with AD and PCStudies of associations between LOY and various outcomes hav...

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“…Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD) are common neurodegenerative disorders in which their pathogenesis is strongly affected by the oxidative stress and inflammation (Jadidi-Niaragh, Shegarfi, Naddafi, & Mirshafiey, 2012;D.-H. Lee, Gold, & Linker, 2012). ROS and electrophiles induce cellular damage leading to autoimmune disease, cancer, and neurodegenerative disease (J.-M. Lee et al, 2005).…”

Section: The Role Of Dmf In the Modulation Of Immune Cells In The Omentioning

confidence: 99%

Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

Hosseini

Masjedi

Baradaran

et al. 2018

Journal Cellular Physiology

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Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor‐κB translocation, upregulation of nuclear factor erythroid‐derived 2(E2)‐related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.

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The Role of Natural Killer Cells in Alzheimer’s Disease

Cited by 36 publications

References 64 publications

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

Gene expression analysis reveals the dysregulation of immune and metabolic pathways in Alzheimer's disease

Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes

Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

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