Abstract
Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens and cellular debris. Microglia emerge from early erythromyeloid progenitors of the yolk sac and enter the developing brain before the establishment of a fully mature blood–brain barrier. In physiological conditions, during brain development, microglia contribute to CNS homeostasis by supporting cell proliferation of neural precursors. In post-natal life, such cells contribute to preserving the integrity of neuronal circuits by sculpting synapses. After a CNS injury, microglia change their morphology and down-regulate those genes supporting homeostatic functions. However, it is still unclear whether such changes are accompanied by molecular and functional modifications that might contribute to the pathological process. While comprehensive transcriptome analyses at the single-cell level have identified specific gene perturbations occurring in the “pathological” microglia, still the precise protective/detrimental role of microglia in neurological disorders is far from being fully elucidated. In this review, the results so far obtained regarding the role of microglia in neurodegenerative disorders will be discussed. There is solid and sound evidence suggesting that regulating microglia functions during disease pathology might represent a strategy to develop future therapies aimed at counteracting brain degeneration in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.
Highlights
Microglia are resident immune cells of the central nervous system (CNS) that belong to the population of primary innate immune cells (Davalos et al, 2005; Nimmerjahn et al, 2005)
The technology used in this work is the nucleus RNA sequencing but the population of cells assayed in this study was depleted of neuronal nuclear antigen (NEUN)+ and oligodendrocyte transcription factor 2 (OLIG2)+ nuclei; the goal of this study is to capture small groups of microglia subtypes (Gerrits et al, 2021)
A long list of studies highlights the importance of neuroinflammation in virtually all neurodegenerative diseases
Summary
Microglia are resident immune cells of the central nervous system (CNS) that belong to the population of primary innate immune cells (Davalos et al, 2005; Nimmerjahn et al, 2005). Microglia are long-lived cells that arise from a transient hematopoietic wave of erythromyeloid precursor cells emerging in the yolk sac (Ginhoux et al, 2010; Li and Barres, 2018). The healthy adult CNS does not receive further precursors from post-natal hematopoiesis, so these early progenitors can sustain microglia turnover during their lifetime (Ginhoux et al, 2010). Colony-stimulating factor 1 (CSF1) is a hematopoietic cytokine that exerts a crucial role in the activity, survival, and maintenance of microglia. Colony-stimulating factor 1 receptor (CSF1R) is the receptor for interleukin (IL)
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