GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Neurosci Lett. 2012 Jun 14;518(1):49-54. doi: 10.1016/j.neulet.2012.04.054. Epub 2012 May 4.
Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28±0.47 vs. 1.06±0.32, p=0.02; and 1.38±0.75 vs. 1.00±0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET.
特发性震颤（ET）是最常见的神经退行性疾病之一。在 ET 患者的大脑中发现浦肯野细胞轴突肿胀（鱼雷）的数量显著增加。我们最近证明，ET 中的鱼雷含有异常积聚的无组织神经丝（NF）蛋白。这就提出了一个问题，即在 ET 病例和对照组之间，小脑组织中的 NF 蛋白组成和/或磷酸化状态是否存在差异。我们使用 Western blot 分析比较了 47 例 ET 病例与 26 例对照（2:1 比例）小脑组织中 NF 轻链（NF-L）、NF 中链（NF-M）、NF 重链（NF-H）和α-中间丝蛋白的水平和磷酸化状态。然而，ET 病例的 SMI-31 水平（即磷酸化 NF-H）和 SMI-32 水平（即非磷酸化 NF-H）明显高于对照组（1.28±0.47 比 1.06±0.32，p=0.02；和 1.38±0.75 比 1.00±0.42，p=0.006）。我们观察到的异常磷酸化状态是否是 ET 中 NF 缺陷轴突运输和/或功能的原因尚不清楚。在几种神经退行性疾病中已经证明了 NF 异常。无论这些蛋白聚集体是这些疾病的原因还是后果，NF 异常已被证明是几种神经退行性疾病中观察到的细胞破坏的重要因素。因此，进一步分析这些 NF 异常及其机制对于增强我们对 ET 发病机制的理解非常重要。
