Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration
Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration
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DOI：
10.1097/00005072-199907000-00006
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发表时间：
1999-07-01
影响因子：
3.2
通讯作者：
Kuncl, RW
中科院分区：
文献类型：
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作者：
Bilak, MM;Corse, AM;Kuncl, RW
虽然色素上皮衍生因子（PEDF）是一种神经营养因子，可能有助于相邻神经视网膜的发育，分化和存活，PEDF mRNA在中枢神经系统中的广泛分布表明，该因子可能对非视网膜神经元具有多效性神经营养和神经保护作用。我们检测了PEDF mRNA及其转录本在脊髓中的分布。通过免疫组织化学和蛋白质印迹分析，使用已知特异性的抗人PEDF抗血清，我们发现，PEDF蛋白存在于脊髓，脑脊液和骨骼肌，其mRNA出现集中在运动神经元的人脊髓。这些观察结果表明，PEDF可能对运动神经元具有潜在的自分泌和旁分泌作用，以及靶源性。我们分析了PEDF在运动神经元变性的出生后器官型培养模型中的药理学效用，并证明其具有高度的神经保护作用。该效应具有生物学意义，显著保留了脊髓的大体器官型形态学外观并保留了运动神经元胆碱乙酰转移酶（ChAT）。单独的PEDF没有增加ChAT，表明观察到的效果是神经保护性的，而不仅仅是运动神经元ChAT的上调。此外，PEDF保存运动神经元数量，证明了存活效应。我们假设PEDF可能在脊髓运动神经元的生存和维持中发挥重要作用，以保护其免受产后获得性损伤。它应进一步发展为运动神经元疾病，如肌萎缩侧索硬化症（ALS）的治疗策略。
Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that may aid the development, differentiation, and survival of adjacent neural retinae, the wider distribution of PEDF mRNA in the central nervous system suggested to us that this factor could have pleiotropic neurotrophic and neuroprotective effects on nonretinal neurons. We examined the distribution of PEDF mRNA and its transcript in the spinal cord. By immunohistochemistry and western blot analysis using an antihuman PEDF antiserum of known specificity, we found that PEDF protein is present in spinal cord, cerebrospinal fluid, and skeletal muscle and that its mRNA appears concentrated in motor neurons of the human spinal cord. These observations indicate that PEDF could have potential autocrine and paracrine effects on motor neurons, as well as being target-derived. We analyzed the pharmacologic utility of PEDF in a postnatal organotypic culture model of motor neuron degeneration and proved it is highly neuroprotective. The effect was biologically important, significantly sparing the spinal cord's gross organotypic morphological appearance and preserving motor neuron choline acetyltransferase (ChAT). PEDF alone did not increase ChAT, indicating that the observed effect is neuroprotective, not merely an upregulation of motor neuron ChAT. Further, PEDF preserved motor neuron number, proving a survival effect. We hypothesize that PEDF may play important roles in the survival and maintenance of spinal motor neurons in their neuroprotection against acquired insults in postnatal life. It should be developed further as a therapeutic strategy for motor neuron diseases such as amyotrophic lateral sclerosis (ALS).