Hasegawa M, Arai T, Ihara Y
2nd Laboratory of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.
Neuron. 1990 Jun;4(6):909-18. doi: 10.1016/0896-6273(90)90144-5.
To test the hypothesis that cortical neurons undergo massive sprouting in Alzheimer's disease brain, we investigated whether neurofibrillary tangles contain fetal antigens. Two monoclonal antibodies to tangles specifically labeled an approximately 300 kd protein in the neonatal brain homogenate, which was subsequently identified as MAP5 (MAP1B). Conversely, two monoclonal antibodies to MAP5 were found to stain tangles. All four reacted with only a phosphorylated species of MAP5. By careful immunochemical analysis, at least three independent phosphorylated epitopes that should have distinct conformations were shown to be shared by tangles and MAP5. However, several monoclonal antibodies to nonphosphorylated MAP5 did not stain tangles. From these observations, we conclude that fragments of phosphorylated MAP5 are bound to tangles. Since MAP5, in particular, a phosphorylated species, is known to be involved in neurite outgrowth, this result supports the sprouting hypothesis.
为了验证阿尔茨海默病大脑中皮质神经元会发生大量发芽的假说，我们研究了神经原纤维缠结是否包含胎儿抗原。两种针对缠结的单克隆抗体在新生脑匀浆中特异性标记了一种约300kd的蛋白质，该蛋白质随后被鉴定为MAP5（MAP1B）。相反，发现两种针对MAP5的单克隆抗体可使缠结染色。所有这四种抗体仅与磷酸化形式的MAP5发生反应。通过仔细的免疫化学分析，发现缠结和MAP5共享至少三个具有不同构象的独立磷酸化表位。然而，几种针对非磷酸化MAP5的单克隆抗体并未使缠结染色。基于这些观察结果，我们得出结论，磷酸化MAP5的片段与缠结结合。由于已知MAP5，特别是磷酸化形式，参与神经突生长，因此该结果支持发芽假说。
