A novel bibenzyl compound (20C) protects mice from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid toxicity by regulating the a-synuclein-related inflammatory response

Abstract

The novel bibenzyl compound 2-[4-hydroxy-3-(4- hydroxyphenyl) benzyl]-4-(4- hydroxyphenyl) phenol (20C) plays a neuroprotective role in vitro, but its effects in vivo have not yet been elucidated. In this study, we estimated the efficacy of 20C in vivo using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) mouse model from behavior, dopamine, and neuron and then the possible mechanisms for these effects were further investigated. The experimental results showed that 20C improved behavioral deficits, attenuated dopamine depletion, reduced dopaminergic neuron loss, protected the blood-brain barrier (BBB) structure, ameliorated a-synuclein dysfunction, suppressed glial activation, and regulated both nuclear factor-kB (NF-kB) signaling and the NOD-like receptor protein (NLRP) 3 inflammasome pathway. Our results indicated that 20C may prevent neurodegeneration in the MPTP/p mouse model by targeting a-synuclein and regulating a-synuclein-related inflammatory responses, including BBB damage, glial activation, NF-kB signaling, and the NLRP3 inflammasome pathway.