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Neuroprotective effect of β-lapachone in MPTP-induced parkinson’s disease mouse model: Involvement of astroglial p-AMPK/Nrf2/HO-1 signaling pathways

Title
Neuroprotective effect of β-lapachone in MPTP-induced parkinson’s disease mouse model: Involvement of astroglial p-AMPK/Nrf2/HO-1 signaling pathways
Authors
Park J.-S.Leem Y.-H.Park J.-E.Kim D.-Y.Kim H.-S.
Ewha Authors
김희선박진선임예현
SCOPUS Author ID
김희선scopusscopus; 박진선scopus; 임예현scopus
Issue Date
2019
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
Biomolecules and Therapeutics vol. 27, no. 2, pp. 178 - 184
Keywords
AstrocyteNeuroprotectionNrf2/HO-1 signalingParkinson’s diseaseβ-Lapachone
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS; KCI WOS scopus
Document Type
Article
Abstract
Parkinson’s disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether β-Lapachone (β-LAP), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model. β-LAP reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, β-LAP protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor- 2 (Nrf2) in neurodegenerative diseases, we investigated whether β-LAP induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that β-LAP increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, β-LAP increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). β-LAP also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that β-LAP exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes. © 2019 The Korean Society of Applied Pharmacology.
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DOI
10.4062/biomolther.2018.234
Appears in Collections:
의과대학 > 의학과 > Journal papers
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