Microglia and astrocyte involvement in neurodegeneration and brain cancer

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.

Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice

“…Downregulation of the Wnt/β-catenin signaling pathway triggered pro-inflammatory microglial activation, leading to microglia-mediated neuroinflammation [ 49 ]. Activated microglia secreted various neurotoxic and inflammatory factors, including IL-1β and TNF-α, ultimately leading to hippocampal neuroinflammation and hippocampus-dependent cognitive impairments [ 50 ].…”

Clickable Biomaterials for Modulating Neuroinflammation

“…While inflammation has a negative connotation, immune cell involvement is both necessary and beneficial for early tissue protection in the CNS. In fact, inhibiting immune cell involvement early after CNS injury exacerbates tissue damage [ 19 , 20 , 21 , 22 , 23 , 24 ]. Nonetheless, sustained neuroinflammation at chronic stages also inhibits tissue repair [ 2 , 25 , 26 ].…”

“…This inflammatory environment is potentiated by both resident glial cells and extravasated peripheral immune cells. The primary glial cells known as astrocytes and microglia both directly contribute to the inflammatory milieu and modulate the response of infiltrating peripheral immune cells, namely monocytes/macrophages, T cell, mast cells, and neutrophils [ 24 , 27 ].…”

“…Pro-inflammatory (M1 and A1) phenotypes are activated mainly by pathogens or pro-inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNFα), and interferon-gamma (IFNγ) [ 24 , 33 ]. For microglia/macrophages, the M1 phenotype is characterized by activation of the signal transducer and activator of transcription 1 (STAT1) pathway and expression of pro-inflammatory cytokines such as TNFα; interleukins IL-16, IL-1β, IL-18; and reactive oxygen and nitrogen species [ 2 , 34 , 35 ].…”

RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway

“…In the central nervous system, neuroinflammation characterized by activation of microglia cells is one of the important causes of almost all neurodegenerative diseases and brain cancer ( Glass et al, 2010 ; Yan et al, 2014 ; Mostofa et al, 2017 ; Candido et al, 2021 ; Vandenbark et al, 2021 ). As the most important immune cells in the brain, microglia, which are homologous to peripheral macrophages, have been recognized to be involved in neuroinflammatory responses in brain pathophysiology ( Hickman et al, 2018 ; Stephenson et al, 2018 ).…”