Microglia use TAM receptors to detect and engulf amyloid β plaques

Nature Immunology, Год журнала: 2021, Номер 22(5), С. 586 - 594

Опубликована: Апрель 15, 2021

Язык: Английский

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Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology

Neuron, Год журнала: 2021, Номер 109(8), С. 1283 - 1301.e6

Опубликована: Март 7, 2021

Язык: Английский

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Role of the cGAS–STING pathway in systemic and organ-specific diseases

Nature Reviews Nephrology, Год журнала: 2022, Номер 18(9), С. 558 - 572

Опубликована: Июнь 22, 2022

Язык: Английский

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Emerging roles of innate and adaptive immunity in Alzheimer’s disease

Immunity, Год журнала: 2022, Номер 55(12), С. 2236 - 2254

Опубликована: Ноя. 8, 2022

Язык: Английский

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A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

Microbiome, Год журнала: 2021, Номер 9(1)

Опубликована: Ноя. 11, 2021

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced marked decrease in dietary fiber intake, but potential mechanism linking low intake cognitive impairment poorly understood. Emerging research reported that diversity gut microbiota Western populations significantly reduced. However, it unknown whether fiber-deficient diet (which alters microbiota) could impair cognition functional elements through gut-brain axis. Results In this study, mouse model long-term (15 weeks) deficiency (FD) was used to mimic sustained humans. We found FD mice showed impaired cognition, including deficits object location memory, temporal order ability perform daily living activities. The hippocampal synaptic ultrastructure damaged mice, characterized by widened clefts thinned postsynaptic densities. A proteomic analysis further identified deficit CaMKIId its associated proteins (including GAP43 SV2C) along with neuroinflammation microglial engulfment synapses. also exhibited dysbiosis (decreased Bacteroidetes increased Proteobacteria), which deficits. Of note, rapid differentiating change observed short-term (7 days) before highlighting possible causal impact profile on outcomes. Moreover, compromised intestinal barrier reduced short-chain fatty acid (SCFA) production. exploit these findings for SCFA receptor knockout oral supplementation verified playing critical role altered impairment. Conclusions This first time, reports fiber-deprived leads altering microbiota-hippocampal axis, pathologically distinct from normal aging. These alert adverse function, highlight increase as nutritional strategy reduce risk developing diet-associated decline

Язык: Английский

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COVID-19-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Barrier Relevance

Cells, Год журнала: 2020, Номер 9(11), С. 2360 - 2360

Опубликована: Окт. 27, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human that has sparked global pandemic of the disease 2019 (COVID-19). The virus invades cells through angiotensin-converting enzyme (ACE2) receptor-driven pathway, primarily targeting tract. However, emerging reports neurological manifestations demonstrate neuroinvasive potential SARS-CoV-2. This review highlights possible routes by which SARS-CoV-2 may invade central nervous system (CNS) and provides insight into recent case COVID-19-associated disorders, namely ischaemic stroke, encephalitis, encephalopathy, epilepsy, neurodegenerative diseases, inflammatory-mediated disorders. We hypothesize neuroinvasion, neuroinflammation, blood-brain barrier (BBB) dysfunction be implicated in development observed disorders; however, further research critical to understand detailed mechanisms pathway infectivity behind CNS pathogenesis.

Язык: Английский

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Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease

Cells, Год журнала: 2022, Номер 11(12), С. 1885 - 1885

Опубликована: Июнь 10, 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid β (Aβ) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many brain’s immunological cells, specifically microglia astrocytes, are involved in AD pathogenesis. Cells innate immune system play an essential role eliminating pathogens but also regulate brain homeostasis AD. When activated, cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, PANoptosis. The often results release proinflammatory cytokines propagate response eliminate Aβ aggregated Tau proteins. However, chronic neuroinflammation, which result from death, has been linked to diseases worsen Therefore, must be tightly balanced appropriately clear these AD-related structural abnormalities without inducing neuroinflammation. In this review, we discuss responses, inflammatory cytokine secretion as they relate Therapeutic strategies targeting mechanisms will critical consider for future preventive or palliative treatments

Язык: Английский

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Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience

Nature Neuroscience, Год журнала: 2023, Номер 26(5), С. 737 - 750

Опубликована: Апрель 24, 2023

Pathological hallmarks of Alzheimer's disease (AD) precede clinical symptoms by years, indicating a period cognitive resilience before the onset dementia. Here, we report that activation cyclic GMP-AMP synthase (cGAS) diminishes decreasing neuronal transcriptional network myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, part mediated cytosolic leakage mitochondrial DNA. Genetic ablation Cgas mice with tauopathy diminished microglial response, preserved synapse integrity plasticity protected against impairment without affecting pathogenic load. increased, while decreased, MEF2C expression linked to AD. Pharmacological inhibition enhanced restored synaptic integrity, memory, supporting therapeutic potential targeting cGAS-IFN-MEF2C axis improve AD-related pathological insults.

Язык: Английский

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Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Сен. 30, 2021

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to failure multi-organ or death. pathogenesis of SARS-CoV-2 infection is attributed a complex interplay between virus host immune response. It involves activation multiple inflammatory pathways leading hyperinflammation cytokine storm, resulting in tissue damage, distress (ARDS) failure. Accumulating evidence raised concern over long-term health effects COVID-19. Importantly, neuroinvasive potential may have consequences brain. This review provides conceptual framework on how tricks system induce cause disease. We also explore key differences mild COVID-19 its short- effects, particularly human

Язык: Английский

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Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology

Acta Neuropathologica, Год журнала: 2021, Номер 143(1), С. 75 - 91

Опубликована: Ноя. 12, 2021

To better define roles that astrocytes and microglia play in Alzheimer's disease (AD), we used single-nuclei RNA-sequencing to comprehensively characterise transcriptomes astrocyte nuclei selectively enriched during isolation post-mortem from neuropathologically defined AD control brains with a range of amyloid-beta phospho-tau (pTau) pathology. Significant differences glial gene expression (including risk genes expressed both the [CLU, MEF2C, IQCK] [APOE, MS4A6A, PILRA]) were correlated tissue amyloid or pTau expression. The differentially distinct between two cell types pathologies, although common (but cell-type specific) sets pathologies each type. Astrocytes showed enrichment for proteostatic, inflammatory metal ion homeostasis pathways. Pathways phagocytosis, inflammation proteostasis perivascular macrophages greater amyloid, but IL1-related pathway was found specifically association pTau. We also distinguishable sub-clusters characterised by transcriptional signatures related either homeostatic functions Gene co-expression analyses revealed potential functional associations soluble biomarkers (CLU) (GPNMB). Our work highlights responses pathological protein clearance inflammation, as well diversity AD.

Язык: Английский

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