Extracellular
nucleotides and
nucleosides are signalling molecules acting in all tissues and organs, including the central nervous system (CNS). A wide variety of effects, exerted by ecto-
purines, requires that their levels, and
ATP in particular, must be precisely controlled. Under physiological conditions, concentration of ecto-
purines is regulated by a complex cascade of ecto-
enzymes, including ecto-NTPDases (
nucleoside triphosphate diphosphohydrolases), ecto-
NPPs (
nucleotide pyrophosphohydrolases/
phosphodiesterases), ectoalkaline
phosphatases, and ecto-5'nucleotidase.
Adenylate kinase, transferring the
phosphate moiety between
nucleotides, also plays a role in controlling ecto-
purines concentration. Disturbances in the elements of purinergic pathway within the CNS underlie the induction and amplification of many neurological pathologies.
ATP released in bulk from the cells, and not degraded by less efficient or dysfunctional ecto-
nucleotidases, triggers excitotoxic damage and neuro-
inflammation in the brain tissue. High
ATP concentration activating specific receptors has been shown to be involved in various disorders throughout CNS, including
brain injury and
ischemia, neuro-
inflammation,
epilepsy as well as
neuropathic pain and
migraine. Taking the above mentioned influence of
ATP into consideration, the modulation of ecto-NTPDase activity or its site-targeted delivery seems a good therapeutic method. The availability of effective brain-targeted drug-delivery system is one of the most significant challenges facing potential NTPDase-based treatment of CNS disorders. The application of genetically engineered stem cells as carrier vehicles offers a promising strategy for the efficient delivery of the
enzyme to CNS tissues.