Papaverine inhibits α-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson's disease

Yea Hyun Leem, Jin Sun Park, Jung Eun Park, Do Yeon Kim, Jihee Lee Kang, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments. Most PD drugs act by improving motor impairments, whereas very few drugs that efficiently recover PD-related neuropathological features, particularly α-synuclein-related toxicity, have been developed. In this study, we found that papaverine (PAP) attenuated behavioral deficits and protected against nigrostriatal dopaminergic degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) mouse model of PD. Histological analysis of tissue dissected from mice sacrificed nearly 3 weeks after the completion of treatment revealed that PAP significantly ameliorated microglia/astrocyte activation in the striatum and substantia nigra of MPTP/P-treated mice. In addition, PAP diminished α-synuclein expression and aggregation in this model. Furthermore, PAP inhibited the phosphorylation of α-synuclein at serine 129, which may underlie the observed reduction in α-synuclein aggregation. PAP also reduced the expression of matrix metalloproteinase-3 (MMP-3), and the MMP3-positive area co-labeled with thioflavin-S. Taken together, our data suggest that PAP inhibits dopaminergic neuronal cell death and α-synuclein aggregation by suppressing neuroinflammation and MMP-3 expression in the subacute MPTP/P mouse model of PD. Accordingly, PAP may be a promising drug for the treatment of PD.

Original languageEnglish
Article number110576
JournalBiomedicine and Pharmacotherapy
Volume130
DOIs
StatePublished - Oct 2020

Keywords

  • Matrix metalloproteinase-3
  • MPTP/probenecid
  • Neuroinflammation
  • Papaverine
  • Parkinson's disease
  • α-Synuclein

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