Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease |
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Authors: | 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 |
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Affiliation: | Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198, USA. |
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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. |
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