School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, South Korea.
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea.
Mol Brain. 2024 Jul 13;17(1):43. doi: 10.1186/s13041-024-01117-2.
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.
背侧开关蛋白 1（DSP1）是哺乳动物 HMGB1 的同源物，于 1994 年首次被鉴定为背侧共抑制因子。DSP1 含有 HMG 盒结构域，在黑腹果蝇中作为转录调节因子发挥作用。它通过调节基因表达，在胚胎发育中发挥着至关重要的作用，特别是在早期胚胎发生中的背腹模式形成中。此外，DSP1 还参与了各种细胞过程，包括细胞命运决定和组织分化，这些过程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较为充分的研究，但它在成年果蝇大脑中的作用仍知之甚少。在这项研究中，我们通过神经元特异性 DSP1 过表达果蝇来研究 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，这些果蝇还表现出神经肌肉接头（NMJ）缺陷、眼睛变小和酪氨酸羟化酶（TH）阳性神经元减少，表明 DSP1 过表达诱导了神经元毒性。我们的数据表明，DSP1 过表达导致神经元功能障碍和毒性，这表明 DSP1 可能成为神经退行性疾病的潜在治疗靶点。
