Department of Neuropathology, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Neurosci Lett. 2012 Aug 1;522(2):134-8. doi: 10.1016/j.neulet.2012.06.026. Epub 2012 Jun 19.
Incorporation of ubiquitin and ubiquitin-related proteins including p62 into neuronal intranuclear inclusions (NIIs) has been reported in a variety of neurodegenerative diseases. However, involvement of autophagy-specific proteins (NBR1 and LC3) in NIIs has not been mentioned. We immunohistochemically examined the brain of patients with Machado-Joseph disease (MJD; n=5), dentatorubral-pallidoluysian atrophy (DRPLA; n=5) and intranuclear inclusion body disease (INIBD; n=5), using antibodies against ubiquitin, p62, NBR1 and LC3. The proportion of p62-, NBR1- and LC3-positive inclusions relative to the number of ubiquitin-positive inclusions was calculated in each case. NIIs were positive for p62 in MJD (19.3%), DRPLA (49.7%) and INIBD (99.8%). As for autophagy-specific proteins, NIIs were positive for NBR1 in MJD (4.2%), DRPLA (5.5%) and INIBD (13.2%) and negative for LC3 in MJD, DRPLA and INIBD, except for one case of INIBD. These findings suggest that autophagy-lysosome pathway is not involved in the formation/degradation of NIIs.
在多种神经退行性疾病中，已报道泛素和包括 p62 在内的泛素相关蛋白被掺入神经元核内包涵体（NIIs）中。然而，自噬特异性蛋白（NBR1 和 LC3）在 NIIs 中的参与尚未提及。我们使用针对泛素、p62、NBR1 和 LC3 的抗体，对 Machado-Joseph 病（MJD；n=5）、齿状核红核苍白球路易体萎缩症（DRPLA；n=5）和核内包涵体病（INIBD；n=5）患者的大脑进行了免疫组织化学检查。在每种情况下，计算 p62、NBR1 和 LC3 阳性包涵体相对于泛素阳性包涵体数量的比例。MJD（19.3%）、DRPLA（49.7%）和 INIBD（99.8%）的 NIIs 均为 p62 阳性。至于自噬特异性蛋白，MJD（4.2%）、DRPLA（5.5%）和 INIBD（13.2%）的 NIIs 为 NBR1 阳性，而 MJD、DRPLA 和 INIBD 的 LC3 均为阴性，除了一个 INIBD 病例为阳性。这些发现表明自噬-溶酶体途径不参与 NIIs 的形成/降解。
