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http://dx.doi.org/10.4062/biomolther.2018.234

Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways  

Park, Jin-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University)
Leem, Yea-Hyun (Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University)
Park, Jung-Eun (Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University)
Kim, Do-Yeon (Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University)
Kim, Hee-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University)
Publication Information
Biomolecules & Therapeutics / v.27, no.2, 2019 , pp. 178-184 More about this Journal
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 ${\beta}-Lapachone$ (${\beta}-LAP$), 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. ${\beta}-LAP$ 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, ${\beta}-LAP$ 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 ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.
Keywords
${\beta}$-Lapachone; Parkinson's disease; Neuroprotection; Astrocyte; Nrf2/HO-1 signaling;
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