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

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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 languageEnglish (US)
Pages (from-to)9435-9440
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number25
DOIs
StatePublished - 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