Parkinson's disease (PD) is a neurodegenerative disease due to lack of dopamine (DA) in nigrostriatal system resulting from the degeneration and necrosis of dopaminergic neurons. No effective cure has been found. Neurturin (NTN) has been demonstrated to protect mesencephalic dopaminergic neurons specifically. Parkinson's disease was induced in rhesus monkeys by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). Rhesus monkeys were randomly divided into a PD model, NTN treatment and normal control groups. In the NTN treatment group, 1 mg of Pichia pastoris -derived recombinant human NTN was injected into the cerebral ventricles 48 h prior to injection of MPTP. Rhesus monkeys in the PD model group acquired PD symptoms that progressed over time, while monkeys treated with NTN had less apparent or no symptoms. Using fluorospectrophotometry, the dopamine (DA), 5-hydroxytry-ptamine (5-HT) and the 5-hydroxyindoleacetic acid (5-HIAA) in substantia nigra, putamen and caudate nucleus in monkeys from the model group were found to be significantly lower than in the normal control group. No significant differences were found between the NTN treatment and normal control groups, but the contents of DA, 5-HT and 5-HIAA in the NTN treatment group were higher than those observed in the PD model group. A dramatic loss of neurons in the substantia nigra in monkeys in the PD model group was observed by light microscopy, while no obvious loss was observed in the NTN treatment group in which the numbers of neurons were similar to those in normal controls. These results indicate that Pichia pastoris -derived recombinant human NTN can prevent PD symptoms as well as protect dopaminergic neurons and preserve DA content in midbrain substantia nigra in rhesus monkeys exposed to MPTP.
LI Hong-Jun, SU Ting, MA Yan-Bing, HE Zhang-Long, LU Shuai-Yao, DAI Chang-Bai, SUN Mao-Sheng. Protection of Dopaminergic Neurons by Recombinant Neurturin Secreted From Pichia pastoris in a Rhesus Monkey Model of Parkinson's Disease[J]. Progress in Biochemistry and Biophysics,2004,31(8):722-726
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