Shao Charles Y, Crary John F, Rao Chandrakant, Sacktor Todd C, Mirra Suzanne S
Department of Pathology , State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
J Neuropathol Exp Neurol. 2006 Apr;65(4):327-35. doi: 10.1097/01.jnen.0000218441.00040.82.
To study the role of atypical protein kinase C (aPKC) in neurodegenerative disease, we investigated the distribution of PKCiota/lambda, an aPKC isoform, in a variety of tauopathies and alpha-synucleinopathies. Immunohistochemical study revealed PKCiota/lambda within tau-positive neurofibrillary inclusions in Alzheimer disease (AD), progressive supranuclear palsy, corticobasal degeneration (CBD), and Pick disease (PiD), within alpha-synuclein-positive Lewy bodies in idiopathic Parkinson disease and dementia with Lewy bodies, as well as within glial inclusions in multisystem atrophy. We also observed PKCiota/lambda label of actin-rich Hirano bodies in AD, PiD, and elderly individuals. Double immunolabeling and fluorescence resonance energy transfer demonstrated close physical association between PKCiota/lambda and phospho-tau or alpha-synuclein in some neurofibrillary tangles and Lewy bodies. Furthermore, PKCiota/lambda colocalized with p62, a chaperone protein that binds to both aPKC and ubiquitin, in most of these inclusions. PKCiota/lambda also closely associated with the inactivated form of glycogen synthase kinase-3beta, GSK-3beta[ser9]. Together, these findings suggest that PKCiota/lambda may play a role in common mechanisms involving the pathogenesis of neurodegenerative disease.
为研究非典型蛋白激酶C（aPKC）在神经退行性疾病中的作用，我们调查了aPKC亚型PKCiota/lambda在多种tau蛋白病和α-突触核蛋白病中的分布情况。免疫组织化学研究显示，在阿尔茨海默病（AD）、进行性核上性麻痹、皮质基底节变性（CBD）和皮克病（PiD）的tau蛋白阳性神经原纤维包涵体中，在特发性帕金森病和路易体痴呆的α-突触核蛋白阳性路易小体中，以及在多系统萎缩的胶质细胞包涵体中均有PKCiota/lambda。我们还在AD、PiD和老年人中观察到富含肌动蛋白的 Hirano小体有PKCiota/lambda标记。双重免疫标记和荧光共振能量转移显示，在一些神经原纤维缠结和路易小体中，PKCiota/lambda与磷酸化tau蛋白或α-突触核蛋白之间存在紧密的物理关联。此外，在大多数这些包涵体中，PKCiota/lambda与p62共定位，p62是一种伴侣蛋白，可同时结合aPKC和泛素。PKCiota/lambda还与糖原合酶激酶-3β的失活形式GSK-3β[ser9]密切相关。这些发现共同表明，PKCiota/lambda可能在涉及神经退行性疾病发病机制的共同机制中发挥作用。
