UM  > 中華醫藥研究院
N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF
Luo, Dan1; Zhao, Jia1; Cheng, Yuanyuan1; Lee, Simon Ming-Yuen2; Rong, Jianhui1
2018-03
Source PublicationMOLECULAR NEUROBIOLOGY
ISSN0893-7648
Volume55Issue:3Pages:2258-2267
AbstractInsufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days. Animal motor functions were assessed by rotarod test and pole test. Our results showed that PACA ameliorated motor impairments in MPTP-challenged mice. Based on Western blot analysis and/or immunofluorescence staining of NGF and tyrosine hydroxylase (TH), PACA preserved TH levels in the midbrain substantia nigra pars compacta. PACA also increased NGF expression while it decreased proNGF accumulation. Interestingly, NGF was widely induced in the midbrains including astrocytes. To elucidate the mechanisms by which PACA induces NGF, we focused on the effects of PACA on two neurotrophic signaling pathways, the PI3K and MEK pathways. We found that PACA induced the phosphorylation of Akt, ERK, and CREB against MPTP-mediated alterations. Importantly, PACA increased NGF levels and subsequently induced TrkA activation in MPTP-treated mice. Consistently, PACA also increased NGF levels in dopaminergic PC12 cells and primary rat midbrain neurons against N-methyl-4-phenylpyridinium iodide (MPP+) toxicity. ERK and PI3K inhibitors attenuated the effects of PACA on NGF levels. Collectively, our results suggest that PACA may rescue NGF insufficiency via sequential activation of PI3K/Akt, ERK1/2, and CREB signaling pathways.
KeywordParkinson's disease Neuroprotection N-propargyl caffeamide (PACA) NGF/TrkApathway PI3K/Akt ERK1/2
DOI10.1007/s12035-017-0486-6
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000426897800035
PublisherHUMANA PRESS INC
Fulltext Access
Citation statistics
Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, 10 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China;
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
Recommended Citation
GB/T 7714
Luo, Dan,Zhao, Jia,Cheng, Yuanyuan,et al. N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF[J]. MOLECULAR NEUROBIOLOGY,2018,55(3):2258-2267.
APA Luo, Dan,Zhao, Jia,Cheng, Yuanyuan,Lee, Simon Ming-Yuen,&Rong, Jianhui.(2018).N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF.MOLECULAR NEUROBIOLOGY,55(3),2258-2267.
MLA Luo, Dan,et al."N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF".MOLECULAR NEUROBIOLOGY 55.3(2018):2258-2267.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Luo, Dan]'s Articles
[Zhao, Jia]'s Articles
[Cheng, Yuanyuan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Luo, Dan]'s Articles
[Zhao, Jia]'s Articles
[Cheng, Yuanyuan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Luo, Dan]'s Articles
[Zhao, Jia]'s Articles
[Cheng, Yuanyuan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.