Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease

Eric J. Benner; R. Lee Mosley; Chris J. Destache; Travis B. Lewis; Vernice Jackson-Lewis; Santhi Gorantla; Craig Nemachek; Steven R. Green; Serge Przedborski; Howard E. Gendelman

doi:10.1073/pnas.0400569101

Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease

Eric J. Benner, R. Lee Mosley, Chris J. Destache, Travis B. Lewis, Vernice Jackson-Lewis, Santhi Gorantla, Craig Nemachek, Steven R. Green, Serge Przedborski, Howard E. Gendelman

Department of Pharmacy Practice

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

271 Scopus citations

Abstract

Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantia nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.

Original language	English (US)
Pages (from-to)	9435-9440
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	25
DOIs	https://doi.org/10.1073/pnas.0400569101
State	Published - Jun 22 2004

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Benner, E. J., Mosley, R. L., Destache, C. J., Lewis, T. B., Jackson-Lewis, V., Gorantla, S., Nemachek, C., Green, S. R., Przedborski, S., & Gendelman, H. E. (2004). Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America, 101(25), 9435-9440. https://doi.org/10.1073/pnas.0400569101

Benner, EJ, Mosley, RL, Destache, CJ, Lewis, TB, Jackson-Lewis, V, Gorantla, S, Nemachek, C, Green, SR, Przedborski, S & Gendelman, HE 2004, 'Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 25, pp. 9435-9440. https://doi.org/10.1073/pnas.0400569101

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AU - Mosley, R. Lee

AU - Destache, Chris J.

AU - Lewis, Travis B.

AU - Jackson-Lewis, Vernice

AU - Gorantla, Santhi

AU - Nemachek, Craig

AU - Green, Steven R.

AU - Przedborski, Serge

AU - Gendelman, Howard E.

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AB - Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantia nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.

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Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease

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