Janke C, Gärtner U, Holzer M, Arendt T
Paul Flechsig Institute of Brain Research, Department Neuroanatomy, University of Leipzig, Germany.
J Hirnforsch. 1998;39(2):143-53.
Alzheimer's disease (AD) is histopathologically characterised by the formation of neurofibrillary tangles (NFTs) that are largely composed of hyperphosphorylated tau protein (PHF-tau), and senile plaques which contain aggregates of the Abeta peptide. Formation of PHF-tau and amyloidogenic processing of the amyloid precursor protein (APP) might be related to a disturbance in the balance between protein phosphorylation and dephosphorylation. In the present study, the effects of injections into the cerebral cortex of either okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, or saline were investigated. Both kinds of injections induced a reversible phosphorylation of tau, albeit to a different extent. The secretion of soluble APP was reduced after OA but not affected after injection of saline. It is concluded that phosphorylation of tau, similar though not identical to those seen in AD can be induced in vivo by inhibition of protein dephosphorylation as well as by unspecific lesion of cortical neurones. It might, therefore, be suggested that phosphorylation processes involved in PHF-formation in AD similarly reflect a neuronal response to injury.
阿尔茨海默病（AD）的组织病理学特征是形成主要由高度磷酸化的tau蛋白（PHF-tau）组成的神经原纤维缠结（NFTs），以及含有β淀粉样肽聚集体的老年斑。PHF-tau的形成和淀粉样前体蛋白（APP）的淀粉样生成过程可能与蛋白质磷酸化和去磷酸化之间的平衡紊乱有关。在本研究中，研究了向大脑皮层注射蛋白磷酸酶1和2A的抑制剂冈田酸（OA）或生理盐水的效果。两种注射均诱导了tau的可逆磷酸化，尽管程度不同。OA注射后可溶性APP的分泌减少，但注射生理盐水后不受影响。结论是，抑制蛋白质去磷酸化以及皮质神经元的非特异性损伤均可在体内诱导tau的磷酸化，这种磷酸化与AD中所见的相似但不完全相同。因此，可能提示AD中PHF形成所涉及的磷酸化过程同样反映了神经元对损伤的反应。
