The overexpression of DSP1 in neurons induces neuronal dysfunction and neurodegeneration phenotypes in Drosophila.

IF 3.3 3区 医学 Q2 NEUROSCIENCES
Si-Eun Baek, Younghwi Kwon, Jong-Won Yoon, Hyo-Sung Kim, Jae-Yoon Yang, Dong-Seok Lee, Eunbyul Yeom
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引用次数: 0

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.

神经元中 DSP1 的过表达会诱导果蝇出现神经元功能障碍和神经退化表型。
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-box 结构域,是黑腹果蝇的转录调节因子。它通过调控基因表达,在胚胎发育过程中,尤其是在早期胚胎发育的背腹形态形成过程中发挥着至关重要的作用。此外,DSP1 还与多种细胞过程有关,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 在胚胎发育过程中的功能已经得到了相对充分的研究,但它在成年果蝇大脑中的作用却仍然鲜为人知。在这项研究中,我们利用神经元特异性 DSP1 过表达果蝇研究了 DSP1 在大脑中的作用。我们观察到,DSP1过表达果蝇的攀爬能力和寿命都有所下降。此外,这些蝇表现出神经肌肉接头(NMJ)缺陷、眼球缩小和酪氨酸羟化酶(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过表达会导致神经元功能障碍和毒性,从而将DSP1定位为神经退行性疾病的潜在治疗靶点。
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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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