Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways
10.4062/biomolther.2018.234
- Author:
Jin Sun PARK
1
;
Yea Hyun LEEM
;
Jung Eun PARK
;
Do Yeon KIM
;
Hee Sun KIM
Author Information
1. Department of Molecular Medicine, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea. hskimp@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
β-Lapachone;
Parkinson's disease;
Neuroprotection;
Astrocyte;
Nrf2/HO-1 signaling
- MeSH:
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
- From:Biomolecules & Therapeutics
2019;27(2):178-184
- CountryRepublic of Korea
- Language:English
-
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.
