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首页> 外文期刊>Nature >Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo
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Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

机译：新型神经营养因子CDNF在体内保护和拯救中脑多巴胺神经元

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In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolution-arily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopa-minergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.
机译：在帕金森氏病中，脑多巴胺神经元在黑质中最明显地退化。神经营养因子促进发育中和成年脊椎动物神经系统中神经元的存活，分化和维持。迄今为止，对多巴胺神经元最有效的神经营养因子是神经胶质细胞系衍生的神经营养因子（GDNF）。在这里，我们确定了保守的多巴胺神经营养因子（CDNF）作为多巴胺神经元的营养因子。 CDNF及其先前描述的脊椎动物和无脊椎动物同种中脑-星形胶质细胞衍生的神经营养因子，是一种分泌的蛋白质，具有八个保守的半胱氨酸残基，预测独特的蛋白质折叠并定义了一个新的，进化上保守的蛋白质家族。 CDNF（Armetl1）在小鼠和人类的几种组织中表达，包括小鼠胚胎和出生后的大脑。在体内，CDNF在帕金森氏病大鼠实验模型中阻止了6-羟基多巴胺（6-OHDA）诱导的多巴矿能神经元变性。在6-OHDA递送至纹状体之前单次注射CDNF可以显着降低苯丙胺诱导的同侧转弯行为，并几乎完全拯救了黑质中的多巴胺能酪氨酸羟化酶阳性细胞。在6-OHDA给药四周后，纹状体内注射CDNF能够恢复多巴胺能神经元功能并防止黑质中多巴胺能神经元变性。因此，在两个实验设置中，CDNF至少都与GDNF一样有效。我们的结果表明CDNF可能对帕金森氏病的治疗有益。

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