Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer’s Disease

Frederiksen, Henriette R.; Haukedal, Henriette; Freude, Kristine

doi:10.1155/2019/7420189

Cited by 53 publications

(40 citation statements)

References 174 publications

(197 reference statements)

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“…Innate immunity primarily recognizes gut microbes by pathogen-associated molecular patterns (PAMPs), which are PRRs. The stimulation of PAMPs such as TLR-2 is responsible for hippocampal neurogenesis, while TLR-4 exhibits the opposite mechanisms ( 22 ). TLR-4 is involved in the development of learning and memory ( 23 ), and inhibits retinal neurogenesis and differentiation through pathways mediated by myeloid differentiation primary response protein (MYD)-88 and nuclear factor-κB (NF-κB) ( 24 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

et al. 2020

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The microbiota-gut-brain axis is considered a central regulator of the immune system after acute ischemic stroke (AIS), with a potential role in determining outcome. Several pathways are involved in the evolution of gut microbiota dysbiosis after AIS. Brain-gut and gut-brain signaling pathways involve bidirectional communication between the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, the enteric nervous system, and the immune cells of the gut. Alterations in gut microbiome can be a risk factor and may also lead to AIS. Both risk factors for AIS and gut-microbiome composition are influenced by similar factors, including diabetes, hypertension, hyperlipidemia, obesity, and vascular dysfunction. Furthermore, the systemic inflammatory response after AIS may yield liver, renal, respiratory, gastrointestinal, and cardiovascular impairment, including the multiple organ dysfunction syndrome. This review focus on biochemical, immunological, and neuroanatomical modulation of gut microbiota and its possible systemic harmful effects after AIS, as well as the role of ischemic stroke on microbiota composition. Finally, we highlight the role of gut microbiota as a potential novel therapeutic target in acute ischemic stroke.

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Section: Pathophysiologymentioning

confidence: 99%

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

et al. 2020

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“…Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs), present on the surface of microglia (Bsibsi et al, 2002;Olson and Miller, 2004;Frederiksen et al, 2019). TLR4, for which the gram-negative bacterial cell wall component lipopolysaccharide (LPS) is a strong agonist, is well known for its role in inflammation, providing many opportunities for therapeutics (Jack et al, 2005;Lu et al, 2008;Roy et al, 2016).…”

mentioning

confidence: 99%

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Gilchrist

Goudarzi

Hafizi

2020

Front. Cell. Neurosci.

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Background: Microglia are well known key regulators of neuroinflammation which feature in multiple neurodegenerative disorders. These cells survey the CNS and, under inflammatory conditions, become "activated" through stimulation of toll-like receptors (TLRs), resulting in changes in morphology and production and release of cytokines. In the present study, we examined the roles of the related TAM receptors, Mer and Axl, and of their ligand, Gas6, in the regulation of microglial pro-inflammatory TNF-α production and microglial morphology. Methods: Primary cultures of murine microglia of wild-type (WT), Mer −/− and Axl −/− backgrounds were stimulated by the TLR4 agonist, lipopolysaccharide (LPS) with or without pre-treatment with Gas6. Gene expression of TNF-α, Mer, and Axl was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) was used to measure TNF-α release from microglia. Immunofluorescence staining of β-actin and the microglial marker Iba1 was performed to reveal microglial morphological changes, with cellular characteristics (area, perimeter, Feret's diameter, minimum Feret, roundness, and aspect ratio) being quantified using ImageJ software. Results: Under basal conditions, TNF-α gene expression was significantly lower in Axl −/− microglia compared to WT cells. However, all microglial cultures robustly responded to LPS stimulation with the upregulation of TNF-α expression to similar degrees. Furthermore, Mer receptor expression was less responsive to LPS stimulation when in Axl knockout cells. The presence of Gas6 consistently inhibited the LPS-induced upregulation of TNF-α in WT, Mer −/− and Axl −/− microglia. Moreover, Gas6 also inhibited LPS-induced changes in the microglial area, perimeter length, and cell roundness in wild-type cells.

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“…Meanwhile, levels of hippocampal LPS in advanced AD cases can be up to 26-fold higher than in cognitively normal age-matched controls [ 41 , 48 ]. LPS localizes in high levels with Aβ1-40/42 in Aβ lesions, around cerebral vessels, and inside oligodendrocytes and neurons in the brain of AD patients [ 49 ]. LPS contributes to myelin injury and white matter hyperintensities, a main pathophysiological feature that is associated with the severity of neurodegeneration and cognitive decline in AD.…”

Section: The Mechanism Underlying Ad Developmentmentioning

confidence: 99%

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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The astronomical increase of the world’s aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer’s Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target various the underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.

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Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer’s Disease

Cited by 53 publications

References 174 publications

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

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