Microglia states and nomenclature: A field at its crossroads

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3458 - 3483

Published: Nov. 1, 2022

Language: Английский

---

Synergy between amyloid-β and tau in Alzheimer’s disease

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(10), P. 1183 - 1193

Published: Aug. 10, 2020

Language: Английский

---

ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease

Antioxidants, Journal Year: 2020, Volume and Issue: 9(8), P. 743 - 743

Published: Aug. 13, 2020

Neurodegenerative disorders, such as Alzheimer’s disease, are a global public health burden with poorly understood aetiology. Neuroinflammation and oxidative stress (OS) undoubtedly hallmarks of neurodegeneration, contributing to disease progression. Protein aggregation neuronal damage result in the activation disease-associated microglia (DAM) via damage-associated molecular patterns (DAMPs). DAM facilitate persistent inflammation reactive oxygen species (ROS) generation. However, mechanisms linking OS have not been well-defined; thus targeting these cells for clinical benefit has possible. In microglia, ROS generated primarily by NADPH oxidase 2 (NOX2) NOX2 is associated DAMP signalling, amyloid plaque deposition, especially cerebrovasculature. Additionally, originating from both NOX mitochondria may act second messengers propagate immune activation; intracellular signalling underlie excessive OS. Targeting key kinases inflammatory response could cease promote tissue repair. Expression antioxidant proteins dehydrogenase 1 (NQO1), promoted transcription factor Nrf2, which functions control limit Lipid droplet accumulating (LDAM) also represent double-edged sword neurodegenerative sequestering peroxidised lipids non-pathological ageing but becoming dysregulated pro-inflammatory disease. We suggest that future studies should focus on targeted manipulation understand driving inflammatory-related activation. Finally, we discuss recent evidence therapeutic target identification be unbiased founded relevant pathophysiological assays discovery translatable anti-inflammatory therapeutics.

Language: Английский

---

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2452 - 2468.e16

Published: June 13, 2022

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection found white-matter-selective in mice humans. Following mild mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused neurogenesis. Concordantly, humans lasting post-COVID exhibit levels. Compared SARS-CoV-2, influenza similar patterns reactivity, oligodendrocyte loss, at early time points, but after influenza, only pathology persisted. These findings illustrate neuropathophysiology cancer therapy may contribute to impairment following even COVID.

Language: Английский

---

Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

Language: Английский

---

ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Nov. 8, 2022

Alzheimer's disease (AD) is the most common cause of dementia worldwide, and its prevalence rapidly increasing due to extended lifespans. Among number genetic risk factors identified, apolipoprotein E (APOE) gene remains strongest prevalent, impacting more than half all AD cases. While ε4 allele APOE significantly increases risk, ε2 protective relative ε3 allele. These alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function mediate lipid transport in brain periphery; however, additional functions diverse biological have been recognized. Pathogenically, seeds amyloid-β (Aβ) plaques with apoE4 driving earlier abundant amyloids. ApoE also differential effects on multiple Aβ-related or Aβ-independent pathways. complexity biology pathobiology presents challenges designing effective apoE-targeted therapeutic strategies. This review examines key pathobiological pathways related targeting strategies a specific focus latest technological advances tools.

Language: Английский

---

White matter aging drives microglial diversity

Neuron, Journal Year: 2021, Volume and Issue: 109(7), P. 1100 - 1117.e10

Published: Feb. 19, 2021

Language: Английский

---

Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases

Science, Journal Year: 2020, Volume and Issue: 370(6512), P. 66 - 69

Published: Oct. 2, 2020

Dementia is a rapidly rising global health crisis that silently disables families and ends lives livelihoods around the world. To date, however, no early biomarkers or effective therapies exist. It now clear brain microglia are more than mere bystanders amyloid phagocytes; they can act as governors of neuronal function homeostasis in adult brain. Here, we highlight fundamental role tissue-resident macrophages health. Then, suggest how chronic impairment microglia-neuron cross-talk may secure permanence failure synaptic Alzheimer's Parkinson's diseases. Understanding to assess modulate interactions critical for will be key developing dementia.

Language: Английский

---

Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 70, P. 101397 - 101397

Published: June 30, 2021

An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor Alzheimer's disease (AD) but holistic view interacting processes through which such may contribute to AD pathogenesis missing. We addressed this need extensive analysis published studies investigating effects western (WD) on development humans laboratory animals. reviewed WD-induced systemic alterations comprising metabolic changes, induction obesity adipose tissue inflammation, gut microbiota dysbiosis acceleration low-grade inflammation. Next we provide an overview evidence demonstrating that WD-associated drive impairment blood-brain barrier (BBB) neuroinflammation paralleled by accumulation toxic amyloid. Later these changes are followed dysfunction synaptic transmission, neurodegeneration finally memory cognitive impairment. conclude WD can trigger inflammaging, BBB induced inflammation play central role process. Moreover, concurrence Aβ dyshomeostasis, reciprocal interactions vicious cycle neurodegeneration, contradicts as primary AD. Given 2019 World Health Organization recommended focusing modifiable factors prevention, sequential, complex pathomechanisms initiated WD, lead from peripheral disturbances support future prevention strategies.

Language: Английский

---

The landscape of aging

Science China Life Sciences, Journal Year: 2022, Volume and Issue: 65(12), P. 2354 - 2454

Published: Sept. 2, 2022

Language: Английский

---