PDF(Pubmed)
Abstract：
Dorsal switch protein 1(DSP1), a mammalian homolog of HMGB1, is firstly identified as a dorsal co-repressor in 1994. DSP1 contains HMG-box domain and functions as a transcriptional regulator in Drosophila melanogaster. It plays a crucial role in embryonic development, particularly in dorsal-ventral patterning during early embryogenesis, through the regulation of gene expression. Moreover, DSP1 is implicated in various cellular processes, including cell fate determination and tissue differentiation, which are essential for embryonic development. While the function of DSP1 in embryonic development has been relatively well-studied, its role in the adult Drosophila brain remains less understood. In this study, we investigated the role of DSP1 in the brain by using neuronal-specific DSP1 overexpression flies. We observed that climbing ability and life span are decreased in DSP1-overexpressed flies. Furthermore, these flies demonstrated neuromuscular junction (NMJ) defect, reduced eye size and a decrease in tyrosine hydroxylase (TH)-positive neurons, indicating neuronal toxicity induced by DSP1 overexpression. Our data suggest that DSP1 overexpression leads to neuronal dysfunction and toxicity, positioning DSP1 as a potential therapeutic target for neurodegenerative diseases.
摘要：
背侧开关蛋白1(DSP1),HMGB1的哺乳动物同系物,在1994年首先被鉴定为背侧共阻遏物。DSP1包含HMG-box结构域，并在果蝇中充当转录调节因子。它在胚胎发育中起着至关重要的作用，特别是在早期胚胎发生过程中的背腹侧模式，通过基因表达的调控。此外，DSP1涉及各种细胞过程，包括细胞命运决定和组织分化，对胚胎发育至关重要。虽然DSP1在胚胎发育中的功能已经得到了相对充分的研究，它在成年果蝇大脑中的作用尚不清楚。在这项研究中,我们通过使用神经元特异性DSP1过表达果蝇研究了DSP1在大脑中的作用。我们观察到DSP1过表达的果蝇的攀爬能力和寿命降低。此外，这些苍蝇表现出神经肌肉接头（NMJ）缺陷，减小的眼睛大小和酪氨酸羟化酶（TH）阳性神经元的减少，表明DSP1过表达诱导的神经元毒性。我们的数据表明，DSP1过表达导致神经元功能障碍和毒性，将DSP1定位为神经退行性疾病的潜在治疗靶点。
