SUN11602, a novel bFGF mimetic, exerts neuroprotective effects in Parkinson's disease

Abstract

Parkinson's disease (PD) is the second most frequent neurodegenerative disease, with a large prevalence in industrialized countries. The etiopathogenesis of PD is multifactorial and not yet fully known, however, in the last few decades, scientific world advised the establishment of a neuroinflammatory state among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor 1 (bFGF/FGFR1) could be a promising way to treat CNS‐mediated inflammation; however, the use of bFGF as a therapeutic agent is limited by its side effects.The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF, but demonstrating greater safety, thus constituting a potential candidate for the treatment of neurodegenerative diseases including PD. In this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP‐induced PD. PD was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1, 2.5, and 5 mg/kg) was administered daily by oral gavage starting from 24 hours after the first administration of MPTP, mice were sacrificed 7 days after MPTP induction. The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF‐kB pathway and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca2+ overload in neurons by regulating Ca2+‐binding proteins, inhibiting the apoptotic cascade. Therefore, considering these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.