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

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260 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

Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. / Benner, Eric J.; Mosley, R. Lee; Destache, Chris J.; Lewis, Travis B.; Jackson-Lewis, Vernice; Gorantla, Santhi; Nemachek, Craig; Green, Steven R.; Przedborski, Serge; Gendelman, Howard E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 25, 22.06.2004, p. 9435-9440.

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

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

Benner, Eric J. ; Mosley, R. Lee ; Destache, Chris J. ; Lewis, Travis B. ; Jackson-Lewis, Vernice ; Gorantla, Santhi ; Nemachek, Craig ; Green, Steven R. ; Przedborski, Serge ; Gendelman, Howard E. / Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 25. pp. 9435-9440.

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AU - Gorantla, Santhi

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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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