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

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

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

Topics: Biological Sciences
Publisher: National Academy of Sciences
Year: 2004
DOI identifier: 10.1073/pnas.0400569101
OAI identifier: oai:pubmedcentral.nih.gov:438994
Provided by: PubMed Central
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