-
International Journal of Molecular... Jan 2024The temporal and spatial pattern of microglia colonization and vascular infiltration of the nervous system implies critical associated roles in early stages of nervous... (Review)
Review
The temporal and spatial pattern of microglia colonization and vascular infiltration of the nervous system implies critical associated roles in early stages of nervous system development. Adding to existing reviews that cover a broad spectrum of the various roles of microglia during brain development, the current review will focus on the developmental ontogeny and interdependency between the colonization of the nervous system with yolk sac derived macrophages and vascularization. Gaining a better understanding of the timing and the interdependency of these two processes will significantly contribute to the interpretation of data generated regarding alterations in either process during early development. Additionally, such knowledge should provide a framework for understanding the influence of the early gestational environmental and the impact of genetics, disease, disorders, or exposures on the early developing nervous system and the potential for long-term and life-time effects.
Topics: Microglia; Macrophages; Yolk Sac; Brain
PubMed: 38279280
DOI: 10.3390/ijms25021281 -
Biomolecules Mar 2021Lysosomes are cellular organelles that contain various acidic digestive enzymes. Despite their small size, they have multiple functions. Lysosomes remove or recycle... (Review)
Review
Lysosomes are cellular organelles that contain various acidic digestive enzymes. Despite their small size, they have multiple functions. Lysosomes remove or recycle unnecessary cell parts. They repair damaged cellular membranes by exocytosis. Lysosomes also sense cellular energy status and transmit signals to the nucleus. Glial cells are non-neuronal cells in the nervous system and have an active role in homeostatic support for neurons. In response to dynamic cues, glia use lysosomal pathways for the secretion and uptake of regulatory molecules, which affect the physiology of neighboring neurons. Therefore, functional aberration of glial lysosomes can trigger neuronal degeneration. Here, we review lysosomal functions in oligodendrocytes, astrocytes, and microglia, with emphasis on neurodegeneration.
Topics: Animals; Astrocytes; Humans; Lysosomes; Microglia; Neurodegenerative Diseases; Neuroglia; Oligodendroglia
PubMed: 33803137
DOI: 10.3390/biom11030400 -
Brain Research Bulletin Jul 2023Microglia, the resident myeloid cells of the central nervous system, are the first line of defense against foreign pathogens, thereby confining the extent of brain... (Review)
Review
Microglia, the resident myeloid cells of the central nervous system, are the first line of defense against foreign pathogens, thereby confining the extent of brain injury. However, the role of microglia is not limited to macrophage-like functions. In addition to proinflammatory response mediation, microglia are involved in neurodevelopmental remodeling and homeostatic maintenance in the absence of disease. An increasing number of studies have also elucidated microglia-mediated regulation of tumor growth and neural repair in diseased brains. Here, we review the non-proinflammatory roles of microglia, with the aim of promoting a deeper understanding of the functions of microglia in healthy and diseased brains and contributing to the development of novel therapeutics that target microglia in neurological disorders.
Topics: Humans; Microglia; Brain; Central Nervous System; Macrophages; Nervous System Diseases
PubMed: 37192719
DOI: 10.1016/j.brainresbull.2023.110664 -
Current Opinion in Neurobiology Oct 2010Microglial cells constitute the resident immune cell population of the mammalian central nervous system. One striking feature of these cells is their highly dynamic... (Review)
Review
Microglial cells constitute the resident immune cell population of the mammalian central nervous system. One striking feature of these cells is their highly dynamic nature under both normal and pathological brain conditions. The highly branched processes of resting microglia display a constitutive mobility and undergo rapid directional movement towards sites of acute tissue disruption. Microglia can be converted by a large number of different stimuli to a chronically activated state by signaling through both purinergic and Toll-like receptor systems, among others. Recent work has uncovered some of the mechanisms underlying microglia dynamics and shed new light into the functional significance of this enigmatic member of the glial cell family.
Topics: Animals; Central Nervous System; Humans; Microglia
PubMed: 20705452
DOI: 10.1016/j.conb.2010.07.002 -
Immunology Letters May 2022Recent advances in genetic analysis and intensive research have revealed that microglial cells respond to external stimuli in various ways and adopt diverse states.... (Review)
Review
Recent advances in genetic analysis and intensive research have revealed that microglial cells respond to external stimuli in various ways and adopt diverse states. Herein, we summarize the current knowledge on the possible microglial states during development, homeostasis, and perturbation. These states are characterized either by irreversible cellular changes, such as cell death and cellular senescence, or reversible alterations, triggered by temporary changes in the microenvironment. Subsequently, we discuss the modalities of the transcriptional and functional recovery of microglia from a molecular perspective. An understanding of (ir)reversible changes in their cellular fates or transcriptional states could provide novel options for the treatment of age-related and neurodegenerative disorders.
Topics: Cell Death; Cellular Senescence; Homeostasis; Microglia
PubMed: 35413354
DOI: 10.1016/j.imlet.2022.04.001 -
Clinical and Translational Medicine Nov 2022The central nervous system (CNS) hosts a variety of immune cells, including two distinct macrophage populations: microglia are found in the parenchyma, whereas... (Review)
Review
The central nervous system (CNS) hosts a variety of immune cells, including two distinct macrophage populations: microglia are found in the parenchyma, whereas CNS-associated macrophages (CAMs) cover the CNS interfaces, such as the perivascular spaces, the meninges and the choroid plexus. Recent studies have given novel insights into the nature of CAMs as compared to microglia. In this mini-review, we summarise the current knowledge about the ontogenetic relationship and the underlying mechanism for the establishment of CNS macrophages during development.
Topics: Central Nervous System; Macrophages; Microglia; Meninges; Choroid Plexus
PubMed: 36336786
DOI: 10.1002/ctm2.1096 -
Journal of Neuroinflammation Apr 2019Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or... (Review)
Review
Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction.
Topics: Animals; Encephalitis, Viral; Humans; Microglia
PubMed: 30967139
DOI: 10.1186/s12974-019-1443-2 -
American Journal of Alzheimer's Disease... 2020Alzheimer's disease (AD) is the most common form of dementia, which is characterized by a progressive cognitive decline and senile plaques formed by amyloid β (Aβ).... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia, which is characterized by a progressive cognitive decline and senile plaques formed by amyloid β (Aβ). Microglia are the immune cells of the central nervous system (CNS). Studies have proposed 2 types of microglia, namely, the resident microglia and bone marrow-derived microglia (BMDM). Recent studies suggested that BMDM, not the resident microglia, can phagocytose Aβ, which has a great therapeutic potential in AD. Bone marrow-derived microglia can populate the CNS in an efficient manner and their functions can be regulated by some genes. Thus, methods that increase their recruitment and phagocytosis could be used as a new tool that clears Aβ and ameliorates cognitive impairment. Herein, we review the neuroprotective functions of BMDM and their therapeutic potential in AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Bone Marrow Cells; Humans; Microglia; Neuroprotection; Phagocytosis; Plaque, Amyloid
PubMed: 32536247
DOI: 10.1177/1533317520927169 -
Cells Nov 2021The activation of microglia, the inflammatory cells of the central nervous system (CNS), has been linked to the pathogenesis of Alzheimer's disease and other... (Review)
Review
The activation of microglia, the inflammatory cells of the central nervous system (CNS), has been linked to the pathogenesis of Alzheimer's disease and other neurodegenerative diseases. How microglia sense the changing brain environment, in order to respond appropriately, is still being elucidated. Microglia are able to sense and respond to the mechanical properties of their microenvironment, and the physical and molecular pathways underlying this mechanosensing/mechanotransduction in microglia have recently been investigated. The Hippo pathway functions through mechanosensing and subsequent protein kinase cascades, and is critical for neuronal development and many other cellular processes. In this review, we examine evidence for the potential involvement of Hippo pathway components specifically in microglia in the pathogenesis of Alzheimer's disease. We suggest that the Hippo pathway is worth investigating as a mechanosensing pathway in microglia, and could be one potential therapeutic target pathway for preventing microglial-induced neurodegeneration in AD.
Topics: Alzheimer Disease; Animals; Hippo Signaling Pathway; Humans; Mechanotransduction, Cellular; Microglia; Models, Biological
PubMed: 34831369
DOI: 10.3390/cells10113144 -
Journal of Neurochemistry Nov 2017γ-Secretase is an intramembrane cleaving protease involved in the generation of the Alzheimer's disease (AD)-associated amyloid β peptide (Aβ). γ-Secretase is... (Review)
Review
γ-Secretase is an intramembrane cleaving protease involved in the generation of the Alzheimer's disease (AD)-associated amyloid β peptide (Aβ). γ-Secretase is ubiquitously expressed in different organs, and also in different cell types of the human brain. Besides the involvement in the proteolytic generation of Aβ from the amyloid precursor protein, γ-secretase cleaves many additional protein substrates, suggesting pleiotropic functions under physiological and pathophysiological conditions. Microglia exert important functions during brain development and homeostasis in adulthood, and accumulating evidence indicates that microglia and neuroinflammatory processes contribute to the pathogenesis of neurodegenerative diseases. Recent studies demonstrate functional implications of γ-secretase in microglia, suggesting that alterations in γ-secretase activity could contribute to AD pathogenesis by modulation of microglia and related neuroinflammatory processes during neurodegeneration. In this review, we discuss the involvement of γ-secretase in the regulation of microglial functions, and the potential relevance of these processes under physiological and pathophysiological conditions. This article is part of the series "Beyond Amyloid".
Topics: Amyloid Precursor Protein Secretases; Animals; Humans; Inflammation; Inflammation Mediators; Microglia; Neurodegenerative Diseases
PubMed: 28940294
DOI: 10.1111/jnc.14224