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 α-synuclein dysfunction, suppressed glial activation, and regulated both nuclear factor-κB (NF-κB) 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 α-synuclein and regulating α-synuclein–related inflammatory responses, including BBB damage, glial activation, NF-κB signaling, and the NLRP3 inflammasome pathway.
Footnotes
- Received July 16, 2017.
- Accepted September 12, 2017.
This work was supported by the National Natural Science Foundation of China [Grants 81773925, U1402221, 81573640, and 81603316], the Beijing Natural Science Foundation [Grant 7161011], the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences [Grant 2016-I2M-1-004], the Key Research and Development Project of Hunan Province [Grant 2015SK2029-1], and the Scientific Research Foundation of the Higher Education Institutions of Hunan Province [Grant 15K091].
- Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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