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; Leem, Yea-Hyun; Park, Jung-Eun; Kim, Do-Yeon; Kim, Hee-Sun

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자료유형: 학술저널

저자정보: 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)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제27권 제2호

발행연도: 2019.1

수록면: 178 - 184 (7page)

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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.

#${beta}$-Lapachone #Parkinson's disease #Neuroprotection #Astrocyte #Nrf2/HO-1 signaling

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