Biomol Ther.  2019 Feb;27(2):178-184. 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

Affiliations
  • 1Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea. hskimp@ewha.ac.kr

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)-immuno-reactive 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.

Keyword

β-Lapachone; Parkinson's disease; Neuroprotection; Astrocyte; Nrf2/HO-1 signaling

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Adenosine
Animals
Astrocytes
Blotting, Western
Brain
DNA
Dopaminergic Neurons
Lymphoma, B-Cell
Mice*
Neurodegenerative Diseases
Neurons
Neuroprotection
Neuroprotective Agents*
Parkinson Disease*
Pars Compacta
Phosphorylation
Protein Kinases
Rotarod Performance Test
Substantia Nigra
Trees
Tyrosine 3-Monooxygenase
Up-Regulation
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Adenosine
DNA
Neuroprotective Agents
Protein Kinases
Tyrosine 3-Monooxygenase
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