Despite major advances in a variety of neuroscientific research fields, the majority of neurodegenerative and neurological diseases are poorly controlled by currently available drugs, which are largely based on a neurocentric drug design. Research from the past five years has established a central role of glia to determine how neurons function and – consequently – glial dysfunction is implicated in almost every neurodegenerative and neurological disease. Glial cells are key regulators of the brain’s endogenous neuroprotectant and anticonvulsant adenosine. This review will summarize how glial cells contribute to adenosine homeostasis and how glial adenosine receptors affect glial function. We will then move on to discuss how glial cells interact with neurons and the vasculature and outline new methods to study glial function. We will discuss how glial control of adenosine-function affects neuronal cell death and its implications for epilepsy, traumatic brain injury, ischemia, and Parkinson’s disease. Eventually, glial adenosine-modulating drug targets might be an attractive alternative for the treatment of neurodegenerative diseases. There are, however, several major open questions that remain to be tackled.
Keywords: astrocyte, adenosine receptor, adenosine kinase, epilepsy, excitotoxicity, neurodegeneration