Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease
Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease
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DOI：
10.1073/pnas.0400569101
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发表时间：
2004-06-22
影响因子：
11.1
通讯作者：
Gendelman, HE
中科院分区：
文献类型：
--
作者：
Benner, EJ;Mosley, RL;Gendelman, HE
黑质纹状体多巴胺能通路的退化是帕金森病的标志，可以在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）中毒的小鼠中重现。在此，我们证明，过继转移共聚物-1免疫细胞MPTP受体小鼠导致大量黑质内的T细胞积累，抑制小胶质细胞活化，并增加星形胶质细胞相关的胶质细胞系衍生的神经营养因子的局部表达。这种免疫策略导致黑质纹状体神经元对MPTP诱导的神经变性的显着保护，该神经变性通过供体T细胞的耗尽而被废除。这种疫苗治疗策略可能对帕金森病有益。
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 substantial 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.