A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease

Zhao, Yan Gang; Zhan, Jicheng; Liu, You‐Shuo

doi:10.14336/ad.2020.0205

Cited by 16 publications

(14 citation statements)

References 142 publications

(175 reference statements)

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“…Immunosenescence is widely used to explain the catastrophic changes that can arise in dementia and the general inability of the elderly to resist immune challenge [ 66 ]. Recent work has indicated that the loss of pineal melatonin may underpin immunosenescence via the lost/suppressed night-time resetting of immune cell metabolism [ 29 ].…”

Section: Circadian Rhythm and Covid-19mentioning

confidence: 99%

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

Anderson¹,

Carbone

Mazzoccoli

2021

IJMS

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The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune responses to SARS-CoV-2 infection. AhR activation dysregulates the initial pro-inflammatory cytokines production driven by neutrophils, macrophages, and mast cells, whilst AhR activation suppresses the endogenous antiviral responses of natural killer cells and CD8+ T cells. Such immune responses become further dysregulated by the increased and prolonged pro-inflammatory cytokine suppression of pineal melatonin production coupled to increased gut dysbiosis and gut permeability. The suppression of pineal melatonin and gut microbiome-derived butyrate, coupled to an increase in circulating lipopolysaccharide (LPS) further dysregulates the immune response. The AhR mediates its effects via alterations in the regulation of mitochondrial function in immune cells. The increased risk of severe/fatal SARS-CoV-2 infection by high risk conditions, such as elderly age, obesity, and diabetes are mediated by these conditions having expression levels of melatonin, AhR, butyrate, and LPS that are closer to those driven by SARS-CoV-2 infection. This has a number of future research and treatment implications, including the utilization of melatonin and nutraceuticals that inhibit the AhR, including the polyphenols, epigallocatechin gallate (EGCG), and resveratrol.

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Section: Circadian Rhythm and Covid-19mentioning

confidence: 99%

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

Anderson¹,

Carbone

Mazzoccoli

2021

IJMS

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“…Thus, the innate cells are probably a cornerstone in driving the fate of immune responsiveness in old age resulting in inflammaging 27 and as such contributing to the development of AD. 65 , 66 …”

Section: Immunosenescence and Inflammaging: A Nutshell Descriptionmentioning

confidence: 99%

“…67,68 In the meantime, the anti-inflammatory mediators such as IL-10, IL-4, IL-13 may also be increased as a tentative measure to control this state. [61][62][63][64][65][66][67][68][69] Latent virus infections such as cytomegalovirus (CMV) infection, as well as commensal bacteria (eg bacteria in gut microbiome dysbiosis), may be reactivated and become harmful and contribute to inflammaging. [70][71][72][73] Indubitably, the finding that noninfectious agents can strongly contribute to the spreading of inflammatory processes has paved the way to extend the list of mechanisms that fuel inflammaging over time.…”

Section: Inflammagingmentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

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Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

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“…Redox imbalance in cells, as well as excessive or unregulated production of inflammatory mediators, is an element of the induction of neurodegenerative diseases, such as atherosclerosis, diabetes, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease [ 28 , 29 , 62 ]. In neurodegenerative diseases, activated microglia is observed, which releases proinflammatory and anti-inflammatory cytokines and neurotoxic mediators.…”

Section: Bioactivity Of Polysaccharides From Ganoderma Lucidummentioning

confidence: 99%

Health-Promoting of Polysaccharides Extracted from Ganoderma lucidum

2021

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Medicinal mushrooms are rich sources of pharmacologically active compounds. One of the mushrooms commonly used in traditional Chinese medicine is Ganoderma lucidum (Leyss. Ex Fr.) Karst. In Asian countries it is treated as a nutraceutical, whose regular consumption provides vitality and improves health. Ganoderma lucidum is an important source of biologically active compounds. The pharmacologically active fraction of polysaccharides has antioxidant, immunomodulatory, antineurodegenerative and antidiabetic activities. In this review, we summarize the activity of Ganoderma lucidum polysaccharides (GLP).

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A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease

Cited by 16 publications

References 142 publications

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Health-Promoting of Polysaccharides Extracted from Ganoderma lucidum

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