Protective effects of Nrf2-ARE activator on dopaminergic neuronal loss in Parkinson disease model mice: Possible involvement of heme oxygenase-1.
Animals
Antioxidant Response Elements
/ drug effects
Cell Death
/ drug effects
Corpus Striatum
/ drug effects
Dopaminergic Neurons
/ drug effects
Heme Oxygenase-1
/ metabolism
Mice
NF-E2-Related Factor 2
/ agonists
Oxidative Stress
/ drug effects
Oxidopamine
Parkinson Disease, Secondary
/ chemically induced
Signal Transduction
/ drug effects
Substantia Nigra
/ drug effects
Up-Regulation
/ drug effects
Antioxidant enzyme
Astrocyte
Nrf2–ARE pathway
Parkinson disease
Journal
Neuroscience letters
ISSN: 1872-7972
Titre abrégé: Neurosci Lett
Pays: Ireland
ID NLM: 7600130
Informations de publication
Date de publication:
25 09 2020
25 09 2020
Historique:
received:
04
05
2020
revised:
09
07
2020
accepted:
20
07
2020
pubmed:
28
7
2020
medline:
1
5
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
Parkinson disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra, and oxidative stress is thought to contribute to this pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is thereby a potential target for therapeutics to reduce neurodegeneration in PD. Previously, we identified TPNA10168 from a chemical library as an activator of the Nrf2-ARE pathway, and the present study examined the effects of TPNA10168 on an in vivo PD model. Subcutaneous administration of TPNA10168 was associated with inhibited dopaminergic neuronal loss and behavioral impairment in 6-hydroxydopamine-induced PD model mice. Heme oxygenase-1 (HO-1) is an antioxidant enzyme expressed downstream of the Nrf2-ARE signaling pathway, and we observed that HO-1 protein levels were upregulated by TPNA10168 in the mouse brain. These results suggest that TPNA10168 inhibits dopaminergic neuronal death in PD model mice, and that upregulation of HO-1 might participate in this effect.
Identifiants
pubmed: 32712353
pii: S0304-3940(20)30538-3
doi: 10.1016/j.neulet.2020.135268
pii:
doi:
Substances chimiques
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Oxidopamine
8HW4YBZ748
Heme Oxygenase-1
EC 1.14.14.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135268Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.