PMID- 32768884
OWN - NLM
STAT- MEDLINE
DCOM- 20210225
LR  - 20210225
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 130
DP  - 2020 Oct
TI  - Papaverine inhibits alpha-synuclein aggregation by modulating neuroinflammation and 
      matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of 
      Parkinson's disease.
PG  - 110576
LID - S0753-3322(20)30769-1 [pii]
LID - 10.1016/j.biopha.2020.110576 [doi]
AB  - 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/P-treated 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.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Leem, Yea-Hyun
AU  - Leem YH
AD  - Department of Molecular Medicine and Medical Research Institute, School of 
      Medicine, Ewha Womans University, Seoul, South Korea.
FAU - Park, Jin-Sun
AU  - Park JS
AD  - Department of Molecular Medicine and Medical Research Institute, School of 
      Medicine, Ewha Womans University, Seoul, South Korea.
FAU - Park, Jung-Eun
AU  - Park JE
AD  - Department of Molecular Medicine and Medical Research Institute, School of 
      Medicine, Ewha Womans University, Seoul, South Korea.
FAU - Kim, Do-Yeon
AU  - Kim DY
AD  - Department of Molecular Medicine and Medical Research Institute, School of 
      Medicine, Ewha Womans University, Seoul, South Korea.
FAU - Kang, Jihee Lee
AU  - Kang JL
AD  - Department of Physiology and Inflammation-Cancer Microenvironment Research 
      Center, School of Medicine, Ewha Womans University, Seoul, South Korea.
FAU - Kim, Hee-Sun
AU  - Kim HS
AD  - Department of Molecular Medicine and Medical Research Institute, School of 
      Medicine, Ewha Womans University, Seoul, South Korea; Department of Brain & 
      Cognitive Sciences, Ewha Womans University, Seoul, South Korea. Electronic 
      address: hskimp@ewha.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20200805
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotoxins)
RN  - 0 (alpha-Synuclein)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - DAA13NKG2Q (Papaverine)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Animals
MH  - Astrocytes/drug effects
MH  - Disease Models, Animal
MH  - Dopaminergic Neurons/drug effects
MH  - MPTP Poisoning/*drug therapy/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice, Inbred C57BL
MH  - Microglia/drug effects
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Neurotoxins
MH  - Papaverine/pharmacology/*therapeutic use
MH  - Protein Aggregation, Pathological/*drug therapy/metabolism
MH  - alpha-Synuclein/metabolism
OTO - NOTNLM
OT  - MPTP/probenecid
OT  - Matrix metalloproteinase-3
OT  - Neuroinflammation
OT  - Papaverine
OT  - Parkinson's disease
OT  - alpha-Synuclein
EDAT- 2020/08/10 06:00
MHDA- 2021/02/26 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/05/28 00:00 [received]
PHST- 2020/07/21 00:00 [revised]
PHST- 2020/07/25 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2021/02/26 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0753-3322(20)30769-1 [pii]
AID - 10.1016/j.biopha.2020.110576 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2020 Oct;130:110576. doi: 10.1016/j.biopha.2020.110576. Epub 
      2020 Aug 5.