Abstract
The brain is unique and the most complex organ of the body, containing neurons and several types of glial cells of different origins and properties that protect and ensure normal brain structure and function. Neurological disorders are the result of a failure of the nervous system multifaceted cellular networks. Although great progress has been made in the understanding of glia involvement in neuropathology, therapeutic outcomes are still not satisfactory. Here, we discuss recent perspectives on the role of microglia and astrocytes in neurological disorders, including the two most common neurodegenerative conditions, Alzheimer disease and progranulin-related frontotemporal lobar dementia, as well as astrocytoma brain tumors. We emphasize key factors of microglia and astrocytic biology such as the highly heterogeneic glial nature strongly dependent on the environment, genetic factors that predispose to certain pathologies and glia senescence that inevitably changes the CNS landscape. Our understanding of diverse glial contributions to neurological diseases can lead advances in glial biology and their functional recovery after CNS malfunction.
Highlights
Brain homeostasis is based on the interplay among all cell types, with microglia and astrocytes subserving a wide array of salient neuronal functions [7]
The much stronger Alzheimer disease (AD) risk factor, APOEε4, has not yet been related to an aged microglia signature. Further studies of this group on aged human samples by single-cell sequencing confirmed the enrichment of microglia subsets involved in interferon response and antigen presentation, as well as genes involved in neurodegenerative diseases with only one particular subtype of microglia that has been changed in AD [71]
It was reported that certain adult brain subpopulations of astrocytes correlated with cellular populations present in highly heterogenous gliomas in mice and humans with increased expression of genes linked to synapse formation [42]
Summary
Brain homeostasis is based on the interplay among all cell types, with microglia and astrocytes subserving a wide array of salient neuronal functions [7]. Human AD pathology in microglia correlated with enrichment in immune/inflammatory pathways, Aβ clearance and genetic risk factors for AD such as TREM2, APOE and the MHC class II genes.
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