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1: Parkinsonism Relat Disord. 2007 Mar;13(2):77-88. Epub 2006 Sep 11.
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Dopaminergic neuroprotection by neurturin-expressing c17.2 neural stem cells in a rat model of Parkinson's disease.

Liu WG, Lu GQ, Li B, Chen SD.

Department of Neurology, Clinical and Research Center for Parkinson Disease and Movement Disorders, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.

Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of regenerative diseases, especially Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor-family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. Here, we have generated a NTN-secreting c17.2 NSC line and investigated the protective effect of NTN-c17.2 on PD rat models. These NTN-releasing NSCs engrafted and integrated in the host striatum with good success, gave rise to neurons, astrocytes and oligodendrocytes, and maintained stable, high-level NTN expression. In addition, inverse transfer of NTN protein into the substantia nigra (SN) was able to protect dopaminergic neurons from 6-OHDA toxicity. Observation of rotational behavior showed that the NTN group performed significantly better than the Mock group, and the protective effect of NTN lasted for at least 4 months. HPLC tests indicated that the contents of neurotransmitters (e.g. dopamine) in the corpus striatum area of the NTN-c17.2 group and the Mock-c17.2 group were significantly higher than in the PBS group, but there was no significant difference between expression in the NTN-c17.2 and Mock-c17.2 groups. Taken together, our results suggest that transplantation of NTN-secreting NSCs exerted protective on PD rat models.

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PMID: 16963309 [PubMed - indexed for MEDLINE]