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Neuroprotective Properties of a Novel Non-Thiazoledinedione Partial PPAR-γ Agonist against MPTP
Joint Authors
Johnson, Jeffrey A.
Johnson, Delinda A.
Emborg, Marina E.
Swanson, Christine R.
Du, Eric
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-10-02
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Activation of the peroxisome proliferator activated receptor-gamma (PPAR)-γ is proposed as a neuroprotective strategy to treat neurodegenerative disorders.
In this study, we examined if LSN862 (LSN), a novel non-thiazoledinedione partial PPAR-γ agonist, was neuroprotective in a mouse model of Parkinson’s disease (PD) and assessed possible mechanisms of action.
LSN (3, 10, or 30 mg/kg) or vehicle was orally administered daily to C57BL/6 and antioxidant response element-human placental alkaline phosphatase (ARE-hPAP) reporter mice 3 days prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, i.p.
× 5 days) or PBS administration.
LSN elicited a dose-dependent preservation of dopaminergic nigrostriatal innervation that was not associated with inhibition of MPTP metabolism or activation of Nrf2-ARE, although changes in NQO1 and SOD2 mRNA were observed.
A significant dose-dependent downregulation in MAC-1 and GFAP positive cells was observed in MPTP + LSN-treated mice as well as significant downregulation of mRNA expression levels of these inflammatory markers.
MPTP-induced increases in PPAR-γ and PGC1α expression were ameliorated by LSN dosing.
Our results demonstrate that oral administration of LSN is neuroprotective against MPTP-induced neurodegeneration, and this effect is associated with downregulation of neuroinflammation, decreased oxidative stress, and modulation of PPAR-γ and PGC1α expression.
These results suggest that LSN can be a candidate alternative non-thiazoledinedione partial PPAR-γ agonist for neuroprotective treatment of PD.
American Psychological Association (APA)
Swanson, Christine R.& Du, Eric& Johnson, Delinda A.& Johnson, Jeffrey A.& Emborg, Marina E.. 2013. Neuroprotective Properties of a Novel Non-Thiazoledinedione Partial PPAR-γ Agonist against MPTP. PPAR Research،Vol. 2013, no. 2013, pp.1-16.
https://search.emarefa.net/detail/BIM-482630
Modern Language Association (MLA)
Swanson, Christine R.…[et al.]. Neuroprotective Properties of a Novel Non-Thiazoledinedione Partial PPAR-γ Agonist against MPTP. PPAR Research No. 2013 (2013), pp.1-16.
https://search.emarefa.net/detail/BIM-482630
American Medical Association (AMA)
Swanson, Christine R.& Du, Eric& Johnson, Delinda A.& Johnson, Jeffrey A.& Emborg, Marina E.. Neuroprotective Properties of a Novel Non-Thiazoledinedione Partial PPAR-γ Agonist against MPTP. PPAR Research. 2013. Vol. 2013, no. 2013, pp.1-16.
https://search.emarefa.net/detail/BIM-482630
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-482630