NT5E and brain disorder: Such threats also require adaptive plastic changes in neuronal circuits, which may explain the increased extracellular formation of ATP-derived adenosine by ecto-nucleotidases, with a burst of its rate-limiting step—ecto-5′-nucleotidase or CD73 (Cunha, 2001)—under noxious brain conditions to sustain an overfunction of A2AR that contributes to synaptotoxicity and neurotoxicity in different brain diseases (Cunha, 2016).