Abstract：
Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient\'s brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.
摘要：
越来越多的证据表明，非神经元少突胶质细胞在肌萎缩侧索硬化症（ALS）和其他神经退行性疾病中起着重要作用。在病人的大脑中，在少突胶质细胞的胞浆中观察到TDP-43，髓鞘结构受损是其病理特征。然而,TDP-43在少突胶质细胞中获得功能的潜在机制，对轴突完整性至关重要，尚不清楚。最近,我们发现截短的TDP-43片段的灵长类动物特异性裂解发生在猴神经细胞的细胞质中。这一发现开辟了研究少突胶质细胞中受致病性TDP-43影响的髓磷脂完整性的途径。在目前的研究中,我们证明了截短的TDP-35在少突胶质细胞中的特异性，可能导致猴call体脱髓鞘功能失调。由于髓鞘调节因子与细胞质中积累的TDP-35相互作用，下游髓磷脂相关基因表达在转录水平下调.我们的研究旨在探讨对髓磷脂结构损伤的潜在影响，受少突胶质细胞中截短的TDP-43的影响，这为TDP-43相关疾病的进行性发病机制和症状的功能获得提供了额外的线索。
