Microglia: Immune and non-immune functions

Immunity, Год журнала: 2021, Номер 54(10), С. 2194 - 2208

Опубликована: Окт. 1, 2021

Язык: Английский

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Remyelination in multiple sclerosis: from basic science to clinical translation

The Lancet Neurology, Год журнала: 2020, Номер 19(8), С. 678 - 688

Опубликована: Июль 20, 2020

Язык: Английский

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TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis

Acta Neuropathologica, Год журнала: 2020, Номер 140(4), С. 513 - 534

Опубликована: Авг. 9, 2020

Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for clearance myelin debris in areas demyelination, a key step to allow remyelination. TREM2 expressed microglia promotes microglial survival, proliferation, phagocytic activity. Herein we demonstrate that was highly on myelin-laden phagocytes active demyelinating lesions CNS subjects with MS. In gene expression studies, macrophages from genetic deficiency displayed defect pathways. Treatment new agonistic antibody promoted cuprizone model demyelination. Effects included enhancement uptake degradation, resulting accelerated removal microglia. Most importantly, antibody-dependent activation increased density oligodendrocyte precursors as well formation mature oligodendrocytes thus enhancing remyelination axonal integrity. These results relevant they propose potential target promote

Язык: Английский

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Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Journal of Neurochemistry, Год журнала: 2019, Номер 151(6), С. 676 - 688

Опубликована: Сен. 3, 2019

The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer's disease is increased age. Therefore, understanding the changes that occur as a result aging central to any possible prevention or cure such conditions. Microglia, resident brain glial population most associated with both protection neurons in health and their destruction disease, could be significant player age related changes. Microglia can adopt an aberrant phenotype sometimes referred either dystrophic senescent. While aged microglia have been frequently identified there no conclusive evidence proves causal role. This has hampered by lack models microglia. We recently generated model senescent based on observation all show iron overload. Iron-overloading cultured causes them take cause neurodegeneration similar those observed patients. review considers how this used determine role diseases.

Язык: Английский

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Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases

Advanced Drug Delivery Reviews, Год журнала: 2019, Номер 165-166, С. 15 - 40

Опубликована: Дек. 6, 2019

Язык: Английский

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Cellular senescence and Alzheimer disease: the egg and the chicken scenario

Nature reviews. Neuroscience, Год журнала: 2020, Номер 21(8), С. 433 - 444

Опубликована: Июнь 29, 2020

Язык: Английский

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Single-cell RNA-seq reveals the transcriptional landscape in ischemic stroke

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2021, Номер 42(1), С. 56 - 73

Опубликована: Сен. 9, 2021

Ischemic stroke (IS) is a detrimental neurological disease with limited treatments options. It has been challenging to define the roles of brain cell subsets in IS onset and progression due cellular heterogeneity CNS. Here, we employed single-cell RNA sequencing (scRNA-seq) comprehensively map populations mouse model MCAO (middle cerebral artery occlusion). We identified 17 principal clusters cell-type specific gene expression patterns as well subpopulations their functions various pathways. The CNS inflammation triggered upregulation key type-specific genes unpublished before. Notably, microglia displayed differentiation diversity after among its five distinct subtypes. Importantly, found potential trajectory branches monocytes/macrophage's subsets. Finally, also subclusters vasculature cells, ependymal cells other glia cells. Overall, scRNA-seq revealed precise transcriptional changes during neuroinflammation at level, opening up new field for exploration mechanisms drug discovery based on cell-subtype molecules.

Язык: Английский

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Neuroinflammation — a common thread in neurological disorders

Nature Reviews Neurology, Год журнала: 2019, Номер 15(8), С. 429 - 430

Опубликована: Июль 1, 2019

Язык: Английский

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Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances

The Lancet Neurology, Год журнала: 2021, Номер 20(6), С. 470 - 483

Опубликована: Апрель 27, 2021

Язык: Английский

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TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination

The Journal of Experimental Medicine, Год журнала: 2021, Номер 218(10)

Опубликована: Авг. 23, 2021

Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of for remyelination is well known, underlying metabolic pathways required debris clearance are poorly understood. Here, we show cholesterol esterification in male mouse microglia/macrophages necessary adaptive to uptake generation lipid droplets upon injury. When droplet biogenesis defective, innate immune cells do not resolve, fails. We found triggering receptor expressed on myeloid 2 (TREM2)–deficient mice unable adapt excess exposure, form fewer droplets, build up endoplasmic reticulum (ER) stress. Alleviating ER stress TREM2-deficient restores resolves response. Thus, conclude TREM2-dependent formation constitute protective occur.

Язык: Английский

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