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

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease.

Original languageEnglish (US)
Article number15010
JournalParkinson's Disease
Volume1
DOIs
StatePublished - 2015

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Oxidopamine
Parkinson Disease
Dopaminergic Neurons
Cell Death
Medial Forebrain Bundle
Amphetamine
Therapeutics
Dopamine
Neurons
Injections
Brain

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

De Jesús-Cortés, H., Miller, A. D., Britt, J. K., DeMarco, A. J., De Jesús-Cortés, M., Stuebing, E., ... Pieper, A. A. (2015). Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease. Parkinson's Disease, 1, [15010]. https://doi.org/10.1038/npjparkd.2015.10

Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease. / De Jesús-Cortés, Héctor; Miller, Adam D.; Britt, Jeremiah K.; DeMarco, Anthony J.; De Jesús-Cortés, Mayralis; Stuebing, Emily; Naidoo, Jacinth; Vázquez-Rosa, Edwin; Morlock, Lorraine; Williams, Noelle S.; Ready, Joseph M.; Narayanan, Nandakumar S.; Pieper, Andrew A.

In: Parkinson's Disease, Vol. 1, 15010, 2015.

Research output: Contribution to journalReview article

De Jesús-Cortés, H, Miller, AD, Britt, JK, DeMarco, AJ, De Jesús-Cortés, M, Stuebing, E, Naidoo, J, Vázquez-Rosa, E, Morlock, L, Williams, NS, Ready, JM, Narayanan, NS & Pieper, AA 2015, 'Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease', Parkinson's Disease, vol. 1, 15010. https://doi.org/10.1038/npjparkd.2015.10
De Jesús-Cortés H, Miller AD, Britt JK, DeMarco AJ, De Jesús-Cortés M, Stuebing E et al. Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease. Parkinson's Disease. 2015;1. 15010. https://doi.org/10.1038/npjparkd.2015.10
De Jesús-Cortés, Héctor ; Miller, Adam D. ; Britt, Jeremiah K. ; DeMarco, Anthony J. ; De Jesús-Cortés, Mayralis ; Stuebing, Emily ; Naidoo, Jacinth ; Vázquez-Rosa, Edwin ; Morlock, Lorraine ; Williams, Noelle S. ; Ready, Joseph M. ; Narayanan, Nandakumar S. ; Pieper, Andrew A. / Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease. In: Parkinson's Disease. 2015 ; Vol. 1.
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abstract = "BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease.",
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AU - De Jesús-Cortés, Héctor

AU - Miller, Adam D.

AU - Britt, Jeremiah K.

AU - DeMarco, Anthony J.

AU - De Jesús-Cortés, Mayralis

AU - Stuebing, Emily

AU - Naidoo, Jacinth

AU - Vázquez-Rosa, Edwin

AU - Morlock, Lorraine

AU - Williams, Noelle S.

AU - Ready, Joseph M.

AU - Narayanan, Nandakumar S.

AU - Pieper, Andrew A.

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N2 - BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease.

AB - BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson's disease.

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