Kawamoto Yasuhiro, Akiguchi Ichiro, Nakamura Shinichi, Honjyo Yasuyuki, Shibasaki Hiroshi, Budka Herbert
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
J Neuropathol Exp Neurol. 2002 Mar;61(3):245-53. doi: 10.1093/jnen/61.3.245.
Several components of Lewy bodies have been identified, but the precise mechanism responsible for the formation of Lewy bodies remains undetermined. The 14-3-3 protein family is involved in numerous signal transduction pathways and interacts with alpha-synuclein, which is a major constituent of Lewy bodies. To elucidate the role of 14-3-3 proteins in neuro-degenerative disorders associated with Lewy bodies, we performed immunohistochemical studies on 14-3-3 in brains from 5 elderly control subjects and from 10 patients with Parkinson disease (PD) or diffuse Lewy body disease (DLBD). In the normal controls, 14-3-3-like immunoreactivity was mainly observed in the neuronal somata and processes in various cortical and subcortical regions. In the PD and DLBD cases, a similar immunostaining pattern was found and immunoreactivity was generally spared in the surviving neurons from the severely affected regions. In addition, both classical and cortical Lewy bodies were intensely immunolabeled and some dystrophic neurites were also immunoreactive for 14-3-3. Our results suggest that 14-3-3 proteins may be associated with Lewy body formation and may play an important role in the pathogenesis of PD and DLBD.
路易小体的几种成分已被确定，但路易小体形成的确切机制仍未明确。14-3-3蛋白家族参与众多信号转导途径，并与α-突触核蛋白相互作用，而α-突触核蛋白是路易小体的主要成分。为阐明14-3-3蛋白在与路易小体相关的神经退行性疾病中的作用，我们对5名老年对照受试者以及10名帕金森病（PD）或弥漫性路易体病（DLBD）患者的大脑进行了14-3-3免疫组化研究。在正常对照中，14-3-3样免疫反应主要见于各皮质和皮质下区域的神经元胞体和突起。在PD和DLBD病例中，发现了类似的免疫染色模式，且在严重受累区域存活的神经元中免疫反应性通常得以保留。此外，经典型和皮质型路易小体均被强烈免疫标记，一些营养不良性神经突对14-3-3也有免疫反应。我们的结果表明，14-3-3蛋白可能与路易小体形成有关，并可能在PD和DLBD的发病机制中起重要作用。
