Distribution of VGF peptides in the human cortex and their selective changes in Parkinson's and Alzheimer's diseases
Distribution of VGF peptides in the human cortex and their selective changes in Parkinson's and Alzheimer's diseases
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DOI：
10.1111/j.1469-7580.2010.01309.x
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发表时间：
2010-12-01
影响因子：
2.4
通讯作者：
Ferri, Gian-Luca
中科院分区：
文献类型：
--
作者：
Cocco, Cristina;D'Amato, Filomena;Ferri, Gian-Luca
VGF mRNA及其前体衍生产物在某些神经元中选择性表达，并迅速响应神经营养因子和神经/电活动。先前的蛋白质组学研究显示，患有阿尔茨海默病和其他疾病的患者脑脊液中一些VGF肽减少，这表明它们具有潜在的诊断和临床意义。由于VGF肽在人类皮层中的存在已经得到了一定程度的阐明，我们在对照受试者和帕金森病患者的死后额叶、顶叶和颞叶皮层区域以及阿尔茨海默病患者的顶叶皮层样本中研究了VGF肽。我们培养了针对proVGF前体蛋白C-/ n端部分、TPGH和TLQP序列以及神经内分泌调节肽(NERP)-1的抗体，所有抗体都用于酶联免疫吸附法结合凝胶层析和免疫组织化学。在对照脑样品中，TPGH和c端肽的含量分别约为130-200和700-2000 pmol g-1， n端和NERP-1肽的含量较少（分别约为10-30和4-20 pmol g-1）， TLQP肽低于检测限。凝胶层析显示，VGF抗血清主要表现为小分子量形式（约0.8-1.3 kDa），而在大鼠和牛脑皮层的不同类型神经元中发现了VGF免疫定位。在帕金森氏症的样本中，顶叶皮层中只有TPGH和NERP-1肽明显减少，而在阿尔茨海默病的样本中，所有的VGF肽都减少。结果提示VGF参与了帕金森病和阿尔茨海默病患者顶叶皮层发生的生理或病理生理机制。
VGF mRNA and its precursor-derived products are selectively expressed in certain neurons and promptly respond to neurotrophins and to neural/electrical activity. Proteomic studies have previously revealed a reduction in some VGF peptides in the cerebrospinal fluid of patients affected by Alzheimer's disease and other conditions, suggesting their potential diagnostic and clinical significance. As the presence of VGF peptides within the human cortex has been somewhat elucidated, they were studied postmortem in the frontal, parietal, and temporal cortex areas of control subjects and patients affected by Parkinson's disease, and in parietal cortex samples from patients with Alzheimer's disease. We raised antibodies to the C-/N-terminal portions of the proVGF precursor protein, to the TPGH and TLQP sequences and to the neuroendocrine regulatory peptide (NERP)-1, all used for enzyme-linked immunosorbent assay coupled with gel chromatography and for immunohistochemistry. In the control brain samples, the levels of TPGH and C-terminus peptides were about 130-200 and 700-2000 pmol g-1, respectively, the N-terminus and NERP-1 peptides were less represented (about 10-30 and 4-20 pmol g-1, respectively), and the TLQP peptides were below detection limits. Upon gel chromatography, the VGF antisera mainly revealed small molecular weight forms (i.e. about 0.8-1.3 kDa), whereas VGF immunolocalisation was found within different types of neuron in rat and bovine brain cortices. In the Parkinson's disease samples, a clear-cut decrease was revealed in the parietal cortex only, exclusively for TPGH and NERP-1 peptides, whereas in the Alzheimer's disease samples, a reduction in all of the VGF peptides was shown. The results suggest the involvement of VGF in the physiological or pathophysiological mechanisms occurring in the parietal cortex of patients with Parkinson's and Alzheimer's diseases.