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Papaverine inhibits alpha-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson's disease
- Title
- Papaverine inhibits alpha-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson's disease
- Authors
- Leem, Yea-Hyun; Park, Jin-Sun; Park, Jung-Eun; Kim, Do-Yeon; Kang, Jihee Lee; Kim, Hee-Sun
- Ewha Authors
- 이지희; 김희선; 박진선; 임예현
- SCOPUS Author ID
- 이지희; 김희선; 박진선; 임예현
- Issue Date
- 2020
- Journal Title
- BIOMEDICINE & PHARMACOTHERAPY
- ISSN
- 0753-3322
1950-6007
- Citation
- BIOMEDICINE & PHARMACOTHERAPY vol. 130
- Keywords
- Parkinson's disease; MPTP/probenecid; alpha-Synuclein; Neuroinflammation; Matrix metalloproteinase-3; Papaverine
- Publisher
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 alpha-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/Ptreated mice. In addition, PAP diminished alpha-synuclein expression and aggregation in this model. Furthermore, PAP inhibited the phosphorylation of alpha-synuclein at serine 129, which may underlie the observed reduction in alpha-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 alpha-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.
- DOI
- 10.1016/j.biopha.2020.110576
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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