Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(8), P. 1197 - 1212.e8

Published: Aug. 1, 2022

Language: Английский

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Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 445 - 465

Published: March 23, 2023

Language: Английский

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APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease

Seminars in Immunology, Journal Year: 2022, Volume and Issue: 59, P. 101594 - 101594

Published: Jan. 1, 2022

Neuroinflammation is a central mechanism involved in neurodegeneration as observed Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), strongest genetic risk factor for AD, directly influences onset and progression by interacting with major pathological hallmarks AD including amyloid-β plaques, neurofibrillary tau tangles, well neuroinflammation. Microglia astrocytes, two immune cells brain, exist an immune-vigilant state providing immunological defense housekeeping functions that promote neuronal well-being. It becoming increasingly evident under conditions, these become progressively dysfunctional regulating metabolic immunoregulatory pathways, thereby promoting chronic inflammation-induced neurodegeneration. Here, we review discuss how APOE specifically APOE4 pathology, disrupts microglial astroglial immunomodulating leading to inflammation contributes AD.

Language: Английский

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Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment

Pharmacological Research, Journal Year: 2022, Volume and Issue: 186, P. 106550 - 106550

Published: Nov. 11, 2022

Chronic, excessive neuroinflammation is a key feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's (PD). However, neuroinflammatory pathways have yet to be effectively targeted in clinical treatments for diseases. Interestingly, increased inflammation risk been associated with type 2 diabetes mellitus (T2DM) insulin resistance (IR), suggesting that mitigate T2DM pathology may successful treating well. Glucagon-like peptide-1 (GLP-1) an incretin hormone promotes healthy signaling, regulates blood sugar levels, suppresses appetite. Consequently, numerous GLP-1 receptor (GLP-1R) stimulating drugs developed approved by the US Food Drug Administration (FDA) related global regulatory authorities treatment T2DM. Furthermore, GLP-1R anti-inflammatory, neurotrophic, neuroprotective properties disorder preclinical models, hence hold promise repurposing In this review, we discuss pathways, intersections between neuroinflammation, brain IR, diseases, focus on AD PD. We additionally overview current FDA-approved agents development, including unimolecular single, dual, triple agonists, highlight those trials treatment. propose already-approved agonists safe, efficacious, cost-effective strategy ameliorating PD quelling neuroinflammation.

Language: Английский

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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

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Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like mice

Cell Reports, Journal Year: 2022, Volume and Issue: 41(4), P. 111532 - 111532

Published: Oct. 1, 2022

The function and regulation of different heterogeneous reactive states astrocytes in depression remain unclear. Here, we demonstrate that neurotoxic (A1-like) are strongly induced, prior to behavioral impairments dendritic atrophy, depression-like mice. More interestingly, global or microglia-specific knockout Nod-like receptor protein 3 (Nlrp3) markedly mitigates A1-like astrocyte induction, whereas astrocyte-specific Nlrp3 depletion is ineffective. Microglial ablation also alleviates the neuronal dysfunction induced by both vitro vivo. We further show microglia NF-κB pathway activates NLRP3 inflammasome which turn caspase-1 induce secretion A1 inductors, leading production astrocytes. Altogether, this study reveals microglial induction via activating neuroinflammatory response chronic stress suggests a potential therapeutic strategy for depression.

Language: Английский

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Lipid-accumulated reactive astrocytes promote disease progression in epilepsy

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(4), P. 542 - 554

Published: March 20, 2023

Language: Английский

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Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 10, 2022

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed information processing and memory. This long-COVID cognitive syndrome shares many features with the cancer therapy-related (CRCI). Neuroinflammation, particularly microglial reactivity consequent dysregulation hippocampal neurogenesis oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute persistent symptoms associated even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by - without neuroinvasion effects on oligodendroglial lineage. Using a mouse model induced intranasal delivery, found white matter-selective reactivity, pattern observed Human brain tissue from 9 individuals COVID-19 or exhibits same prominent reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among chemokines demonstrating elevation CCL11, which impairments function. Humans experiencing (48 subjects) similarly demonstrate CCL11 levels compared those who lack (15 subjects). Impaired neurogenesis, decreased oligodendrocytes myelin loss subcortical matter evident 1 week, persisted until 7 weeks, following mice. Taken together, findings presented here illustrate striking similarities between neuropathophysiology after therapy infection, elucidate deficits lasting

Language: Английский

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Advancing cell therapy for neurodegenerative diseases

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 512 - 529

Published: April 20, 2023

Language: Английский

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Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(11), P. 4781 - 4789

Published: Aug. 10, 2022

Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied associations cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like 1 (YKL-40) levels with amyloid-β (Aβ) tau pathologies. We assessed 121 individuals across aging AD clinical spectrum positron emission tomography (PET) imaging for Aβ ([

Language: Английский

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