Your browser doesn't support javascript.
loading
Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways
Biomolecules & Therapeutics ; : 178-184, 2019.
Article in English | WPRIM | ID: wpr-739660
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Parkinson Disease / Phosphorylation / Protein Kinases / Trees / Tyrosine 3-Monooxygenase / Brain / DNA / Substantia Nigra / 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Adenosine Type of study: Prognostic study Limits: Animals Language: English Journal: Biomolecules & Therapeutics Year: 2019 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Main subject: Parkinson Disease / Phosphorylation / Protein Kinases / Trees / Tyrosine 3-Monooxygenase / Brain / DNA / Substantia Nigra / 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Adenosine Type of study: Prognostic study Limits: Animals Language: English Journal: Biomolecules & Therapeutics Year: 2019 Type: Article