Astroglial contribution to tau-dependent neurodegeneration

Astrocytes, by maintaining an optimal environment for neuronal function, play a critical role in proper function of mammalian nervous system. They regulate synaptic transmission and plasticity and protect neurons against toxic insults. Astrocytes and neurons interact actively via glutamine-glutamate cycle (GGC) that supports neuronal metabolic demands and neurotransmission. GGC deficiency may be involved in different diseases of the brain, where impaired astrocytic control of glutamate homeostasis contributes to neuronal dysfunction. This includes tau-dependent neurodegeneration, where astrocytes lose key molecules involved in regulation of glutamate/glutamine homeostasis, neuronal survival and synaptogenesis. Astrocytic dysfunction in tauopathy appears to precede neurodegeneration and overt tau neuropathology such as phosphorylation, aggregation and formation of neurofibrillary tangles. In this review, we summarize recent studies demonstrating that activation of astrocytes is strictly associated with neurodegenerative processes including those involved in tau related pathology. We propose that astrocytic dysfunction, by disrupting the proper neuron-glia signalling early in the disease, significantly contributes to tauopathy pathogenesis.