4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0400569101

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Funding

  1. NCRR NIH HHS [P20 RR015635, P20RR15635] Funding Source: Medline
  2. NIA NIH HHS [R01 AG021617] Funding Source: Medline
  3. NIMH NIH HHS [P01 MH64570, P01 MH064570] Funding Source: Medline
  4. NINDS NIH HHS [2R37 NS36126, P01 NS11766, 1T32 NS07488, P50 NS 38370, P50 NS038370, R01 NS38586, R01 NS 42269, R01 NS038586, R01 NS042269, T32 NS007488, P01 NS011766, R37 NS036126] Funding Source: Medline

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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.

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