Macrophage-mediated GDNF Delivery Protects Against Dopaminergic Neurodegeneration: A Therapeutic Strategy for Parkinson's Disease
MPTP
DOI:
10.1038/mt.2010.107
Publication Date:
2010-06-08T14:47:24Z
AUTHORS (8)
ABSTRACT
Glial cell line-derived neurotrophic factor (GDNF) has emerged as the most potent neuroprotective agent tested in experimental models for treatment of Parkinson's disease (PD). However, its use is hindered by difficulties delivery to brain due presence blood-brain barrier (BBB). In order circumvent this problem, we took advantage fact that bone marrow stem cell-derived macrophages are able pass BBB and home sites neuronal degeneration. Here, report development a method GDNF genetically modified macrophages. Bone cells were transduced ex vivo with lentivirus expressing gene driven synthetic macrophage-specific promoter then transplanted into recipient mice. Eight weeks after transplantation, mice injected neurotoxin, MPTP, 7 days induce dopaminergic neurodegeneration. Macrophage-mediated dramatically ameliorated MPTP-induced degeneration tyrosine hydroxylase (TH)-positive neurons substantia nigra TH(+) terminals striatum, stimulated axon regeneration, reversed hypoactivity open field test. These results indicate macrophage-mediated promising strategy developing therapy PD.
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