Sea Urchin Pigment Ethylspinazarin (U-573): A Novel P2X7 Receptor Antagonist with Neuroprotective and Antiparkinsonian Effects.

The ability of the quinonoid sea urchin pigment ethylspinazarin (U-573) to protect mouse Neuro-2a neuronal cells from the neurotoxic effect of one of the Parkinson's disease inducers, MPP+, was studied. This compound blocked Ca2+ influx and inhibited macropore formation through the P2X7 receptor induced by high concentrations of ATP. Ethylspinazarin at a concentration of 10 μM increased the viability of neuronal cells treated with the neurotoxin by approximately 15% and reduced the level of NO and ROS to control values. Further, U-573 prevented the MPP+-induced formation of amyloid-like protein aggregates in neuronal cells by approximately 50%. This compound at a dosage of 1 mg/kg exerted an anti-inflammatory effect in a mouse model of inflammation, reducing ATP-induced paw edema to values of intact animals. Moreover, the potential of ethylspinazarin in providing an antiparkinsonian effect was shown using a mouse model of MPTP-induced Parkinson's disease. It is likely that the antiparkinsonian activity in in vivo experiments may be mediated by the ability of U-573 to cross the blood-brain barrier. Finally, we found that U-573 effectively inhibits the functioning of ATP-dependent purinergic P2X7 receptors in neuronal cells. This property may be of key importance in the manifestation of the antiparkinsonian activity of this 1,4-naphthoquinone.