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

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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish
Pages (from-to)178-184
Number of pages7
JournalBiomolecules and Therapeutics
Volume27
Issue number2
DOIs
StatePublished - Dec 2019

Keywords

  • Astrocyte
  • Neuroprotection
  • Nrf2/HO-1 signaling
  • Parkinson’s disease
  • β-Lapachone

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