Purine Based Nucleoside Mimetics Library
Purine nucleotides and nucleosides act as extracellular messengers, according to the concept of purinergic signaling first proposed over 30 years ago by Burnstock. The purine nucleoside adenosine plays a neuromodulatory role in the brain. It is directly involved in a number of functions including metabolism, cellular communication, and DNA methylation. Purinergic signaling by adenosine and its metabolites can occur through a variety of receptors and have profound intracellular effects.
The purine nucleoside adenosine, which is involved in energy processes, may also regulate pain processes. Changing the activity of adenosine A3 receptors, which stimulates GABA, also turn off the pain signal. [1]
The purine nucleoside guanosine is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in in vivo and in vitro models of neurotoxicity. Guanosine was reported to prevent seizures induced by the NMDA receptor agonist quinolinic acid and cell death in the rat striatum. Guanosine is also able to modulate glutamate transporter activity by increasing astrocytic glutamate uptake and decreasing glutamate uptake into synaptic vesicle. Guanosine is capable to protect against glutamate-induced cell death in rat hippocampal slices by a mechanism dependent on PI3K/Akt pathway activation, inhibition of GSK-3β, and inducible nitric oxide synthase inhibition. [2]
[1] J. A. Hubbard and D. K. Binder, Adenosine Metabolism. 2016. [2] G. Z. Réus et al., “Glutamatergic NMDA Receptor as Therapeutic Target for Depression,” Adv. Protein Chem. Struct. Biol., vol. 103, pp. 169–202, 2016, doi: 10.1016/bs.apcsb.2015.10.003.