Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism
Entity
UAM. Departamento de BioquímicaPublisher
Mary Ann Liebert, Inc.Date
2011-06-15Citation
10.1089/ars.2010.3731
Antioxidants & Redox Signaling 14.12 (2011): 2347-2360
ISSN
1523-0864DOI
10.1089/ars.2010.3731Funded by
This work was supported by a Target Validation Grant of the Michael J. Fox Foundation for Parkinson’s Research and grant SAF2010-17822 from the Spanish Ministery of Science and Innovation.Editor's Version
http://dx.doi.org/10.1089/ars.2010.3731Subjects
Symptoms of Parkinson’s disease; Therapies; Factor Nrf2; MedicinaNote
This is a copy of an article published in the ANTIOXIDANTS & REDOX SIGNALING (15-08-2011) copyright Mary Ann Liebert, Inc. ANTIOXIDANTS & REDOX SIGNALING is avalaible online at: http://online.liebertpub.comRights
© Mary Ann Liebert, Inc.Abstract
Current therapies for motor symptoms of Parkinson’s disease (PD) are based on dopamine replacement. However,
the disease progression remains unaffected, because of continuous dopaminergic neuron loss. Since oxidative stress is
actively involved in neuronal death in PD, pharmacological targeting of the antioxidant machinery may have
therapeutic value.Here,we analyzed the relevance of the antioxidant phase II responsemediated by the transcription
factor NF-E2-related factor 2 (Nrf2) on brain protection against the parkinsonian toxin methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP). Intraperitoneal administration of the potentNrf2 activator sulforaphane (SFN) increased
Nrf2 protein levels in the basal ganglia and led to upregulation of phase II antioxidant enzymes heme oxygenase-1
(HO-1) and NAD(P)H quinone oxidoreductase (NQO1). In wild-type mice, but not in Nrf2-knockout mice, SFN
protected against MPTP-induced death of nigral dopaminergic neurons. The neuroprotective effects were accompanied
by a decrease in astrogliosis, microgliosis, and release of pro-inflammatory cytokines. These results provide
strong pharmacokinetic and biochemical evidence for activation ofNrf2 and phase II genes in the brain and also offer
a neuroprotective strategy that may have clinical relevance for PD therapy
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Google Scholar:Jaźwa, Agnieszka
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Rojo Sanchís, Ana Isabel
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Innamorato, Nadia G.
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Hesse, Marlen
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Fernández-Ruíz, Javier Javier
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Cuadrado Pastor, Antonio
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