Guanine and isoguanine promote axon regeneration of dorsal root ganglion neurons and survival of retinal ganglion cells after injury

Neurological injuries usually lead to motor, sensory, or cognitive impairment, which urgently need the development of effective therapeutic strategies. An increasing number of studies have indicated that metabolites can serve as therapeutic drugs for treating diseases or repairing damaged tissues. Among them, purines and their derivatives have shown the neuroprotection effects in the nervous system and garnered significant focus in the field of pharmaceutical development. In the present study, we found that the level of isoguanine in the dorsal root ganglion (DRG) was decreased after sciatic nerve injury. Functional investigations revealed that isoguanine and its isomer, guanine, promote axon growth of primary DRG neurons in vitro and enhance axon regeneration in vivo in the peripheral nervous system (PNS) by activating Akt signaling. Conversely, in the central nervous system (CNS), both guanine and isoguanine could not induce the regeneration of the optic nerve; instead, they enhance the survival of retinal ganglion cells after optic nerve crush injury. Collectively, these data provide experimental evidence supporting guanine and isoguanine as promising therapeutic candidates for the management of neurological injuries within both the PNS and CNS.