Vincent I, Zheng J H, Dickson D W, Kress Y, Davies P
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Neurobiol Aging. 1998 Jul-Aug;19(4):287-96. doi: 10.1016/s0197-4580(98)00071-2.
We have shown previously that the TG-3 and MPM-2 antibodies recognize phosphoepitopes common to mitosis and degenerating neurons of Alzheimer's disease(AD) brain. Here, we have evaluated their occurrence in human brain biopsy tissue, and confirm that they are absent in mature neurons of adult brain, but reappear during neurodegeneration in AD. The TG-3 epitope appears ahead of the MPM-2 epitope and is distributed throughout the neuronal soma. Tau is the major TG-3 antigen in AD brain. The initial localization of MPM-2 immunoreactivity in primary dendrites, it's robust occurrence in granulovacuolar bodies, and the increased immunoreactivity with 300-350-kDa proteins, suggest MAPI B as a candidate MPM-2 antigen in AD. Production of mitotic phosphepitopes in more than one type of human neurodegenerative lesion implicates mitotic kinases as common mediators of neuronal death. Because mitotic phosphoepitopes appear before paired helical filaments, it is suggested that mitotic kinase activation triggers neurofibrillary tangle formation. Future studies will need to focus on factors influencing mitotic kinase activity, a point with potential for early diagnosis and disease abrogation.
我们之前已经表明，TG-3和MPM-2抗体识别有丝分裂和阿尔茨海默病（AD）脑退化神经元共有的磷酸化表位。在此，我们评估了它们在人脑活检组织中的出现情况，并证实它们在成人大脑的成熟神经元中不存在，但在AD的神经退行性变过程中重新出现。TG-3表位比MPM-2表位出现得早，且分布于整个神经元胞体。Tau是AD脑中主要的TG-3抗原。MPM-2免疫反应性最初定位于初级树突，在颗粒空泡体中大量出现，以及与300 - 350 kDa蛋白质的免疫反应性增加，提示MAPI B是AD中MPM-2抗原的一个候选物。在不止一种类型的人类神经退行性病变中产生有丝分裂磷酸化表位表明有丝分裂激酶是神经元死亡的常见介质。由于有丝分裂磷酸化表位出现在双螺旋丝之前，提示有丝分裂激酶激活触发神经原纤维缠结形成。未来的研究需要关注影响有丝分裂激酶活性的因素，这一点对于早期诊断和疾病消除具有潜在意义。
