Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)

Eric R. Marcotte; Anita Chugh; Ram K. Mishra; Rodney L. Johnson

doi:10.1016/S0196-9781(97)00321-5

Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH₂ (PLG, MIF-1)

Eric R. Marcotte, Anita Chugh, Ram K. Mishra, Rodney L. Johnson

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH₂ (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF- 1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.

Original language	English (US)
Pages (from-to)	403-406
Number of pages	4
Journal	Peptides
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/S0196-9781(97)00321-5
State	Published - Feb 1998

Bibliographical note

Funding Information:
This work was supported by the NIH, USA, and the Parkinson’s Foundation of Canada.

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

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10.1016/S0196-9781(97)00321-5

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title = "Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)",

abstract = "3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF- 1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.",

author = "Marcotte, {Eric R.} and Anita Chugh and Mishra, {Ram K.} and Johnson, {Rodney L.}",

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AU - Marcotte, Eric R.

AU - Chugh, Anita

AU - Mishra, Ram K.

AU - Johnson, Rodney L.

PY - 1998/2

Y1 - 1998/2

N2 - 3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF- 1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.

AB - 3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF- 1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.

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