Induction of an effective anti-Amyloid-β humoral response in aged mice

Illouz, Tomer; Madar, Ravit; Hirsh, Tamir; Biragyn, Arya; Okun, Eitan

doi:10.1016/j.vaccine.2021.07.023

Cited by 8 publications

(4 citation statements)

References 65 publications

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“…Astrocyte H3K27ac, ACLY, and p300 expression were quantified as previously described 63,64 . Briefly, GFAP-positive cells were detected by implementing the bwlabel algorithm for labeling connected components in 2-D images using MATLAB (MathWorks).…”

Section: Methodsmentioning

confidence: 99%

Disease-associated astrocyte epigenetic memory promotes CNS pathology

Lee,

Rone,

et al. 2024

Preprint

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Astrocytes play important roles in the central nervous system (CNS) physiology and pathology. Indeed, astrocyte subsets defined by specific transcriptional activation states contribute to the pathology of neurologic diseases, including multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). However, little is known about the stability of these disease-associated astrocyte subsets, their regulation, and whether they integrate past stimulation events to respond to subsequent challenges. Here, we describe the identification of an epigenetically controlled memory astrocyte subset which exhibits exacerbated proinflammatory responses upon re-challenge. Specifically, using a combination of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (ATACseq), chromatin immunoprecipitation with sequencing (ChIPseq), focused interrogation of cells by nucleic acid detection and sequencing (FINDseq), and cell-specific in vivo CRISPR/Cas9 based genetic perturbation studies we established that astrocyte memory is controlled by the metabolic enzyme ATP citrate lyase (ACLY), which produces acetyl coenzyme A (acetylCoA) used by the histone acetyltransferase p300 to control chromatin accessibility. ACLY+p300+ memory astrocytes are increased in acute and chronic EAE models; the genetic targeting of ACLY+ p300+ astrocytes using CRISPR/Cas9 ameliorated EAE. We also detected responses consistent with a pro-inflammatory memory phenotype in human astrocytes in vitro; scRNAseq and immunohistochemistry studies detected increased ACLY+ p300+ astrocytes in chronic MS lesions. In summary, these studies define an epigenetically controlled memory astrocyte subset that promotes CNS pathology in EAE and, potentially, MS. These findings may guide novel therapeutic approaches for MS and other neurologic diseases.

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Section: Methodsmentioning

confidence: 99%

Disease-associated astrocyte epigenetic memory promotes CNS pathology

Lee,

Rone,

et al. 2024

Preprint

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“…Due to the inferior induction of cellular and humoral responses to novel antigens, especially if the response is T-cell dependent, aging-related loss in immunological functioning is the primary cause of older people’s decreased protective responses to vaccines [ 77 ]. The need for vaccine strategies to address this issue is growing, especially for active immunotherapy against age-related diseases such as AD [ 77 ].…”

Section: Current Treatment Strategies Targeting Aβmentioning

confidence: 99%

Alzheimer’s Disease: A Brief History of Immunotherapies Targeting Amyloid β

Vogt

Jennings²,

Mohsen

et al. 2023

IJMS

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Alzheimer’s disease (AD) is the most common form of dementia and may contribute to 60–70% of cases. Worldwide, around 50 million people suffer from dementia and the prediction is that the number will more than triple by 2050, as the population ages. Extracellular protein aggregation and plaque deposition as well as accumulation of intracellular neurofibrillary tangles, all leading to neurodegeneration, are the hallmarks of brains with Alzheimer’s disease. Therapeutic strategies including active and passive immunizations have been widely explored in the last two decades. Several compounds have shown promising results in many AD animal models. To date, only symptomatic treatments are available and because of the alarming epidemiological data, novel therapeutic strategies to prevent, mitigate, or delay the onset of AD are required. In this mini-review, we focus on our understanding of AD pathobiology and discuss current active and passive immunomodulating therapies targeting amyloid-β protein.

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“…As time goes by, the cells of the body are undergoing oxidation, aging and replacement at all times since everyone was born (X. Peng et al, 2021). Aging is a process characterized by structural degeneration, decline in body function, immunity and adaptability, because the rate of cell replacement slows down, and the proportion of oxidized and senescent cells in the body gradually increases with the addition of age (Illouz et al, 2021; Li, Hu, et al, 2021; Permatasari et al, 2021). And this process is irreversible.…”

Section: Application Of C Elegans Model To Evaluate Nutrition Of Acti...mentioning

confidence: 99%

Application of Caenorhabditis elegans in the evaluation of food nutrition: A review

Xiao

et al. 2023

eFood

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At present, more and more people are suffering from various diseases and it is particularly important to find a suitable biological model to evaluate the prevention and treatment effects of various drugs and active ingredients on diseases. In all biological models, Caenorhabditis elegans is a kind of organism that is easy to observe and cultivate, has a clear genetic background and a high degree of signal pathway conservation with humans. A variety of active ingredients such as polyphenols, polysaccharides, polypeptides, and vitamins exist from natural products, which has extremely high physiological functions and medicinal values. It is highly reliable to evaluate the trophic and functional properties of the active ingredients from natural products in C. elegans. The functional properties of the active ingredients from natural products such as antiaging, anti-oxidation, regulating lipid metabolism, preventing and treating Alzheimer's disease in C. elegans were clarified in this review. At the same time, its possible pathways were summarized. The literature revealed that it had great effect to evaluate the nutrition and functionality of the active ingredients from natural products in C. elegans. Finally, the shortcomings in this field and suggestions for further improvement in this field have been emphasized.

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Induction of an effective anti-Amyloid-β humoral response in aged mice

Cited by 8 publications

References 65 publications

Disease-associated astrocyte epigenetic memory promotes CNS pathology

Disease-associated astrocyte epigenetic memory promotes CNS pathology

Alzheimer’s Disease: A Brief History of Immunotherapies Targeting Amyloid β

Application of Caenorhabditis elegans in the evaluation of food nutrition: A review

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