Abe Keisuke, Ohkubo Takuya, Yokota Takanori
Department of Neurology and Neurological Science, Tokyo Medical and Dental University.
J Med Dent Sci. 2017;64(1):9-17. doi: 10.11480/jmds.640102.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. A common characteristic of ALS pathology is cytoplasmic inclusions primarily composed of transactive response DNA-binding protein of 43 kDa (TDP-43). Production of TDP-43 in the central nervous system is strictly regulated, but it is not known whether this is also true in the skin of ALS patients. We found a gradual but significant reduction in epidermal TDP-43 mRNA expression with illness progression in ALS patients with upper-limb onset. However, the immunoblotting analysis revealed more TDP-43 protein in the skin of patients with upper-limb onset than of those with other onsets. There was no correlation between the TDP-43 mRNA expression and protein levels, indicating that the mechanism of TDP-43 autoregulation in the patients' skin gradually failed. ALS diagnosis depends on clinical signs and electrophysiological findings, making early diagnosis difficult. TDP-43, as quantified by immunoblot analysis of biopsied skin, is a potential new biomarker of ALS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病。ALS病理学的一个共同特征是细胞质内含物，主要由43 kDa的反式激活应答DNA结合蛋白（TDP-43）组成。中枢神经系统中TDP-43的产生受到严格调控，但尚不清楚在ALS患者的皮肤中是否也是如此。我们发现，上肢起病的ALS患者随着病情进展，表皮TDP-43 mRNA表达逐渐但显著降低。然而，免疫印迹分析显示，上肢起病患者皮肤中的TDP-43蛋白比其他起病患者的更多。TDP-43 mRNA表达与蛋白水平之间无相关性，表明患者皮肤中TDP-43的自我调节机制逐渐失效。ALS的诊断依赖于临床体征和电生理检查结果，使得早期诊断困难。通过对活检皮肤进行免疫印迹分析定量的TDP-43，是一种潜在的ALS新生物标志物。
