Fig. 1

Potential relationships between neurodegenerative diseases and glial cells. The release of aggregated pathogenic proteins such as amyloid-β, tau, α-synuclein, mSOD1, and TDP-43, into the extracellular space drives the changes of microglia and astrocytes into their pro-inflammatory phenotypes. The predominance of the pro-inflammatory phenotype of microglia results in the increase of pro-inflammatory factors and a decrease of the phagocytic effect. The pro-inflammatory-phenotype astrocytes release pro-inflammatory factors, which can dysregulate the synaptic function, the blood-brain barrier, metabolic function, glutamate, extracellular ions, and blood flow. Ultimately, this can lead to neurodegenerative disease progression. A dotted line with a question mark represents a possible relationship, with a lack of evidence for a direct association