Goedert M, Spillantini M G, Jakes R, Crowther R A, Vanmechelen E, Probst A, Götz J, Bürki K, Cohen P
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Neurobiol Aging. 1995 May-Jun;16(3):325-34. doi: 10.1016/0197-4580(95)00017-9.
Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease where their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major fibrous component. Recent work has shown that PHFs are composed of the microtubule-associated protein tau in a hyperphosphorylated state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self-assemble into the PHF. Current evidence suggests that protein kinases or protein phosphatases with a specificity for serine/threonine-proline residues play an important role in the hyperphosphorylation of tau. Candidate protein kinases include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin-dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a candidate phosphatase.
大量神经原纤维缠结、神经毡丝和斑块神经突构成了阿尔茨海默病的神经原纤维病理改变。它们在疾病中发生变性的神经细胞内形成，其区域分布与痴呆程度相关。每个病变都含有双螺旋丝（PHF）作为其主要纤维成分。最近的研究表明，PHF由处于高度磷酸化状态的微管相关蛋白tau组成。PHF-tau在六种成人脑tau异构体上高度磷酸化。因此，tau无法与微管结合，并被认为会自组装成PHF。目前的证据表明，对丝氨酸/苏氨酸-脯氨酸残基具有特异性的蛋白激酶或蛋白磷酸酶在tau的高度磷酸化中起重要作用。候选蛋白激酶包括丝裂原活化蛋白激酶、糖原合酶激酶-3和细胞周期蛋白依赖性激酶5，而蛋白磷酸酶2A的三聚体形式是一种候选磷酸酶。
