Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease

Héctor De Jesús-Cortés; Adam D Miller; Jeremiah K Britt; Anthony J DeMarco; Mayralis De Jesús-Cortés; Emily Stuebing; Jacinth Naidoo; Edwin Vázquez-Rosa; Lorraine Morlock; Noelle S Williams; Joseph M Ready; Nandakumar S Narayanan; Andrew A Pieper

doi:10.1038/npjparkd.2015.10

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Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease

Journal article

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Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease

Héctor De Jesús-Cortés, Adam D Miller, Jeremiah K Britt, Anthony J DeMarco, Mayralis De Jesús-Cortés, Emily Stuebing, Jacinth Naidoo, Edwin Vázquez-Rosa, Lorraine Morlock, Noelle S Williams, …

NPJ Parkinson's Disease, Vol.1(1), p.15010

2015

DOI: 10.1038/npjparkd.2015.10

PMCID: PMC4859442

PMID: 27158662

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Abstract

There are currently no therapeutic options for patients with Parkinson's disease that prevent or slow the death of dopaminergic neurons. We have recently identified the novel P7C3 class of neuroprotective molecules that blocks neuron cell death. The aim of this study was to determine whether treatment with highly active members of the P7C3 series blocks dopaminergic neuron cell death and associated behavioral and neurochemical deficits in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. After unilateral injection of 6-OHDA into the median forebrain bundle, rats were assessed for behavioral function in the open field, cylinder test, and amphetamine-induced circling test. Thereafter, their brains were subjected to neurochemical and immunohistochemical analysis of dopaminergic neuron survival. Analysis was conducted as a function of treatment with P7C3 compounds, with administration initiated either before or after 6-OHDA exposure. Animals administered P7C3-A20 or P7C3-S243, two of the most advanced agents in the P7C3 series of neuroprotective compounds, both before and after 6-OHDA exposure showed evidence of protective efficacy in all measures. When P7C3-S243 administration was initiated after 6-OHDA exposure, rats also showed protective efficacy in all measures, which included blocking dopaminergic neuron cell death in ipsilateral substantia nigra pars compacta, preservation of dopamine and its metabolites in ipsilateral striatum, and preservation of normal motor behavior. The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease.

Details

Title: Subtitle: Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease
Creators: Héctor De Jesús-Cortés - Graduate program of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Adam D Miller - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jeremiah K Britt - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Anthony J DeMarco - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Mayralis De Jesús-Cortés - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Emily Stuebing - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jacinth Naidoo - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Edwin Vázquez-Rosa - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Free Radical and Radiation Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Lorraine Morlock - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Noelle S Williams - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Joseph M Ready - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Nandakumar S Narayanan - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Andrew A Pieper - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Free Radical and Radiation Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; The Iowa City Department of Veterans Affairs, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: NPJ Parkinson's Disease, Vol.1(1), p.15010
DOI: 10.1038/npjparkd.2015.10
PMID: 27158662
PMCID: PMC4859442
NLM abbreviation: NPJ Parkinsons Dis
ISSN: 2373-8057
eISSN: 2373-8057
Publisher: United States
Grant note: T32 CA078586 / NCI NIH HHS P50 CA174521 / NCI NIH HHS
Language: English
Date published: 2015
Academic Unit: Neurology; Psychiatry; Iowa Neuroscience Institute; Radiation Oncology
Record Identifier: 9984020742402771

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