KMID : 0606920190270020178
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Biomolecules & Therapeutics 2019 Volume.27 No. 2 p.178 ~ p.184
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Neuroprotective Effect of ¥â-Lapachone in MPTP-Induced Parkinson¡¯s Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways
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Park Jin-Sun
Leem Yea-Hyun Park Jung-Eun Kim Do-Yeon Kim Hee-Sun
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Abstract
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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 ¥â-Lapachone (¥â-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. ¥â-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, ¥â-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 ¥â-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 ¥â-LAP increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ¥â-LAP increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ¥â-LAP also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ¥â-LAP exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.
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KEYWORD
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¥â-Lapachone, Parkinson¡¯s disease, Neuroprotection, Astrocyte, Nrf2/HO-1 signaling
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