Microglial signatures and their role in health and disease

Nature reviews. Neuroscience, Год журнала: 2018, Номер 19(10), С. 622 - 635

Опубликована: Сен. 11, 2018

Язык: Английский

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Microglia in Alzheimer’s disease

Journal of Clinical Investigation, Год журнала: 2017, Номер 127(9), С. 3240 - 3249

Опубликована: Авг. 31, 2017

Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. express a wide range of receptors act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition their classical cell function, microglia guardians brain by promoting phagocytic clearance providing trophic ensure tissue repair maintain cerebral homeostasis. Conditions associated with loss homeostasis changes induce several dynamic microglial processes, including cellular morphology, surface phenotype, secretory mediators, proliferative responses (referred "activated state"). Activated represent common pathological feature neurodegenerative diseases, Alzheimer's disease (AD). Cumulative evidence suggests inflammatory activity in AD is increased while microglial-mediated mechanisms compromised. perpetually engaged mutual interaction surrounding environment CNS; thus, diverse reactions at different stages may open new avenues for therapeutic intervention modification activities. this Review, role pathogenesis modulation modality will be discussed.

Язык: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Июль 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Язык: Английский

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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

Cell, Год журнала: 2020, Номер 182(4), С. 976 - 991.e19

Опубликована: Июль 22, 2020

Язык: Английский

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Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Март 26, 2018

Abstract Microglia are highly motile glial cells that proposed to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons leads an excess immature connections, thought be the result impaired phagocytosis synapses by microglia. However, until now direct has not been reported fundamental questions remain about precise structures phagocytic mechanisms involved. Here we used light sheet fluorescence microscopy follow microglia–synapse interactions in developing organotypic hippocampal cultures, complemented a 3D ultrastructural characterization using correlative electron (CLEM). Our findings define set dynamic interactions, including selective partial phagocytosis, or trogocytosis ( trogo -: nibble), presynaptic induction postsynaptic spine head filopodia These allow us propose mechanism for facilitatory role remodeling maturation.

Язык: Английский

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