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

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

Research output: Contribution to journalArticle

239 Citations (Scopus)

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
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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Dopaminergic Neurons
Parkinson Disease
Immunization
T-Lymphocytes
Glial Cell Line-Derived Neurotrophic Factor
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Adoptive Transfer
Astrocytes
Vaccines
Therapeutics
4-phenyl-1,2,3,6-tetrahydropyridine
Pars Compacta
Neuroprotection

All Science Journal Classification (ASJC) codes

  • Genetics
  • General

Cite this

Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. / Benner, Eric J.; Mosley, R. Lee; Destache, Christopher 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 journalArticle

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, Christopher 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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