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Genetic heterogeneity within a consanguineous family involving TTPA and SETX genes 一个涉及 TTPA 和 SETX 基因的近亲家族的遗传异质性
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-12-18 DOI: 10.1080/01677063.2023.2281916
Cyrine Jeridi, Amine Rachdi, Fatma Nabli, Zacharia Saied, Rania Zouari, Dina Ben Mohamed, Mariem Ben Said, Saber Masmoudi, Samia Ben Sassi, Rim Amouri
Autosomal recessive cerebellar ataxias (ARCA) constitute a highly heterogeneous group of progressive neurodegenerative disorders that typically occur prior to adulthood. Despite some clinical resem...
常染色体隐性遗传小脑共济失调症(ARCA)是一组高度异质性的进行性神经退行性疾病,通常在成年前发病。尽管在临床上有一些相似之处...
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引用次数: 0
Knockdown of circ_CLIP2 regulates the proliferation, metastasis and apoptosis of glioma cells through miR-641/EPHA3/STAT3 axis. circ_CLIP2的敲除通过miR-641/EPHA3/STAT3轴调节神经胶质瘤细胞的增殖、转移和凋亡。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-09-01 Epub Date: 2023-04-27 DOI: 10.1080/01677063.2023.2199067
Huibing Li, Xin Jin, Mingyao Lai, Yongshi Li, Ruixing Li, Huihui Yang, Baoying Yang

A great amount of reaches have confirmed that circular RNAs (circRNAs) are novel regulators in glioma progression. Here, our work aimed to probe the specific role of circ_CLIP2 in glioma. The mRNA and protein expressions were analyzed by qRT-PCR and western blot, respectively. Cell viability, migration, invasion and apoptosis were examined by MTT assay, tranwell and flow cytometry assays, respectively. Moreover, the binding relationships between circ_CLIP2, microRNA (miR)-641 and erythropoietin-producing human hepatocellular (Eph)A3 were verified by dual luciferase reporter gene assay and/or RIP assay. The following data showed that circ_CLIP2 and EPHA3 were markedly increased in glioma tissues and cells, while miR-647 was downregulated. Gain- and loss-of-function experiments discovered that circ_CLIP2 knockdown remarkably inhibited cell proliferation, migration and invasion and promoted cell apoptosis of glioma cells, while these effects of circ_CLIP2 knockdown were abolished by miR-641 inhibition. Circ_CLIP2 was proved as a sponge of miR-641 to competitively upregulate EPHA3 expression. In addition, EPHA3 overexpression could abolish the inhibitory effects of miR-641 overexpression on the malignant behaviors of glioma cells by activating the signal transducer and activator of transcription 3 (STAT3). These findings elucidated that circ_CLIP2 knockdown suppressed glioma development by regulation of the miR-641/EP HA3/STAT3 axis, which provided a novel mechanism for understanding the pathogenesis of glioma.

大量研究证实,环状RNA(circRNA)是神经胶质瘤进展中的新调节因子。在此,我们的工作旨在探讨circ_CLIP2在神经胶质瘤中的特异性作用。通过qRT-PCR和蛋白质印迹分别分析mRNA和蛋白质的表达。分别用MTT法、Transwell法和流式细胞术检测细胞活力、迁移、侵袭和凋亡。此外,通过双荧光素酶报告基因测定和/或RIP测定验证了circ_CLIP2、微小RNA(miR)-641和产生红细胞生成素的人肝细胞(Eph)A3之间的结合关系。以下数据显示,circ_CLIP2和EPHA3在神经胶质瘤组织和细胞中显著增加,而miR-647下调。功能获得和丧失实验发现,circ_CLIP2敲低显著抑制神经胶质瘤细胞的增殖、迁移和侵袭,并促进细胞凋亡,而circ_CLIP2敲低的这些作用被miR-641抑制所消除。Circ_CLIP2被证明是miR-641的海绵,可竞争性上调EPHA3的表达。此外,EPHA3过表达可以通过激活信号转导子和转录激活子3(STAT3)来消除miR-641过表达对神经胶质瘤细胞恶性行为的抑制作用。这些发现阐明了circ_CLIP2敲低通过调节miR-641/EP HA3/STAT3轴来抑制胶质瘤的发展,这为理解胶质瘤的发病机制提供了一种新的机制。
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引用次数: 0
Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification. 神经干细胞来源的外泌体FTO通过抑制小胶质细胞NRF2 mRNA m6A修饰来保护神经元免受小胶质细胞炎症损伤。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-09-01 Epub Date: 2023-10-16 DOI: 10.1080/01677063.2023.2259995
Zhiyong Li, Zhenggang Chen, Jun Peng

Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.

缺血性中风(IS)可导致神经元细胞损失和功能缺陷。来源于神经干细胞的外泌体(NSC-Exos)改善IS后的神经可塑性并促进神经功能修复。然而,其潜在机制尚不清楚。本研究对NSC外显子进行了表征,并与小胶质细胞共培养。我们发现NSC-Exos在氧-葡萄糖剥夺/复氧和LPS诱导的小胶质细胞中增加了NRF2的表达,并将小胶质细胞从M1促炎表型转化为M2抗炎表型。NSC-Exos通过肥胖相关基因(FTO)减少核因子红系2相关因子2(NRF2)mRNA的m6A甲基化修饰。此外,NSC-Exos减少了小胶质细胞炎症反应对神经元的损伤。最后,小胶质细胞中NRF2过表达减弱了由NSE Exos中FTO敲低引起的小胶质细胞极化和神经元损伤的变化。这些发现表明,NSC-Exos通过转移FTO促进小胶质细胞的NRF2表达和M2极化,从而产生神经保护作用。
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引用次数: 0
The DST gene in neurobiology. 神经生物学中的 DST 基因
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-09-01 Epub Date: 2024-03-11 DOI: 10.1080/01677063.2024.2319880
Robert Lalonde, Catherine Strazielle

DST is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive Dstdt (dystonia musculorum) spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to Dstdt mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous Dst mutations, targeted Dst knockout mice, DstTg4 transgenic mice carrying two deleted Dst exons, DstGt mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific Dst knockout mice. As a result of nerve damage, Dstdt mutants display dystonia and ataxia, as seen in several genetically modified models and their motor coordination deficits have been quantified along with the spontaneous Dst nonsense mutant, the conditional Schwann cell-specific Dst knockout, the conditional DstGt mutant, and the Dst-b isoform specific Dst mutant. Recent findings in humans have associated DST mutations of the Dst-b isoform with hereditary sensory and autonomic neuropathies type 6 (HSAN-VI). These data should further encourage the development of genetic techniques to treat or prevent ataxic and dystonic symptoms.

DST 是一种基因,其替代剪接可产生上皮细胞、神经细胞和肌肉异构体。常染色体隐性遗传的 Dstdt(肌张力障碍)小鼠自发突变会导致脊髓小脑束以及周围感觉神经、背根神经节和颅神经节变性。除 Dstdt 突变体外,轴突病变和神经纤维在神经周围积聚也是其他两个自发性 Dst 突变小鼠品系、靶向 Dst 基因敲除小鼠、携带两个缺失 Dst 外显子的 DstTg4 转基因小鼠、含有肌动蛋白结合域异构体的 DstGt 小鼠和条件性许旺细胞特异性 Dst 基因敲除小鼠的特征。由于神经损伤,Dstdt 突变体表现出肌张力障碍和共济失调,这在几种转基因模型中都可以看到,而且它们的运动协调障碍已经与自发性 Dst 无义突变体、条件性许旺细胞特异性 Dst 基因敲除、条件性 DstGt 突变体和 Dst-b 异构体特异性 Dst 突变体一起进行了量化。最近的人类研究发现,Dst-b 同工型的 DST 突变与遗传性感觉和自主神经病变 6 型(HSAN-VI)有关。这些数据将进一步促进治疗或预防共济失调和肌张力障碍症状的基因技术的发展。
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引用次数: 0
Yin Yang 1 suppresses apoptosis and oxidative stress injury in SH-SY5Y cells by facilitating NR4A1 expression. 阴阳1号通过促进NR4A1的表达来抑制SH-SY5Y细胞的凋亡和氧化应激损伤。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-09-01 Epub Date: 2023-11-03 DOI: 10.1080/01677063.2023.2270745
Qin Kang, Wen Chai, Jun Min, Xinhui Qu

Oxidative stress plays a significant role in the development of Parkinson's disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the NR4A1 promoter. MPP+ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP+-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP+-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with NR4A1 promoter. In addition, in MPP+-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP+-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with NR4A1 promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.HIGHLIGHTSNR4A1 and YY1 are decreased in MPP+-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP+-treated SH-SY5Y cells.YY1 binds with NR4A1 promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.

氧化应激在帕金森病(PD)的发展中起着重要作用。先前的研究表明,核受体亚家族4 A组成员1(NR4A1)与PD相关的氧化应激有关。然而,NR4A1表达调控的分子机制尚不完全清楚。在本研究中,通过在SH-SY5Y细胞中使用1-甲基-4-苯基吡啶鎓(MPP+)建立PD细胞模型。分别用CCK-8法和流式细胞术评估细胞活力和细胞凋亡。LDH和SOD的活性以及ROS的产生被用作氧化应激的指标。ChIP-PCR检测阴阳1(YY1)与NR4A1启动子之间的相互作用。MPP+处理以剂量和时间依赖的方式抑制SH-SY5Y细胞的活力。NR4A1和YY1在MPP+处理的SH-SY5Y细胞中的表达降低。增加NR4A1或YY1可减轻MPP+诱导的SH-SY5Y细胞凋亡和氧化应激,而减少NR4A1可加重MPP+诱发的细胞损伤。转录因子YY1通过与NR4A1启动子结合促进NR4A1的表达。此外,在MPP+处理的SH-SY5Y细胞中,YY1的过表达进一步增强了NR4A1对细胞凋亡和氧化应激的抑制作用。NR4A1的减少导致MPP+诱导的SH-SY5Y细胞中细胞凋亡和氧化应激的升高,YY1的过表达部分逆转了这种作用。总之,YY1通过与NR4A1启动子结合并促进NR4A1的表达来抑制MPP+诱导的SH-SY5Y细胞的凋亡和氧化应激。我们的研究结果表明,NR4A1可能是PD治疗的候选靶点。HIGHGHGHTSNR4A1和YY1在MPP+处理的SH-SY5Y细胞中降低。NR4A1在MPP+处理的SH-SY5Y细胞中防止氧化应激和细胞凋亡。YY1与NR4A1启动子结合并增加NR4A1的表达。YY1增强NR4A1对SH-SY5Y细胞凋亡和氧化应激的抑制作用。
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引用次数: 0
A conserved function of Pkhd1l1, a mammalian hair cell stereociliary coat protein, in regulating hearing in zebrafish. 哺乳动物毛细胞立体纤毛外壳蛋白Pkhd1l1在调节斑马鱼听力中的保守功能。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-09-01 Epub Date: 2023-03-24 DOI: 10.1080/01677063.2023.2187792
Stylianos Makrogkikas, Ruey-Kuang Cheng, Hao Lu, Sudipto Roy

Pkhd1l1 is predicted to encode a very large type-I transmembrane protein, but its function has largely remained obscure. Recently, it was shown that Pkhdl1l1 is a component of the coat that decorates stereocilia of outer hair cells in the mouse ear. Consistent with this localization, conditional deletion of Pkhd1l1 specifically from hair cells, was associated with progressive hearing loss. In the zebrafish, there are two paralogous pkhd1l1 genes - pkhd1l1α and pkhd1l1β. Using CRISPR-Cas9 mediated gene editing, we generated loss-of-function alleles for both and show that the double mutants exhibit nonsense-mediated-decay (NMD) of the RNAs. With behavioural assays, we demonstrate that zebrafish pkhd1l1 genes also regulate hearing; however, in contrast to Pkhd1l1 mutant mice, which develop progressive hearing loss, the double mutant zebrafish exhibited statistically significant hearing loss even from the larval stage. Our data highlight a conserved function of Pkhd1l1 in hearing and based on these findings from animal models, we postulate that PKHD1L1 could be a candidate gene for sensorineural hearing loss (SNHL) in humans.

Pkhd1l1被预测编码一种非常大的I型跨膜蛋白,但其功能在很大程度上仍不清楚。最近,研究表明,Pkhdl1l1是装饰小鼠耳朵外毛细胞立体纤毛的外壳的一种成分。与这种定位一致的是,有条件地从毛细胞中特异性地缺失Pkhd1l1与进行性听力损失有关。在斑马鱼中,有两个同源的pkhd1l1基因——pkhd1llα和pkhd1lβ。使用CRISPR-Cas9介导的基因编辑,我们产生了两者的功能缺失等位基因,并表明双突变体表现出RNA的无义介导衰变(NMD)。通过行为分析,我们证明斑马鱼pkhd1l1基因也调节听力;然而,与出现进行性听力损失的Pkhd1l1突变小鼠相比,双突变斑马鱼甚至从幼虫阶段就表现出统计学上显著的听力损失。我们的数据强调了Pkhd1l1在听力中的保守功能,基于动物模型的这些发现,我们推测Pkhd1l1可能是人类感音神经性听力损失(SNHL)的候选基因。
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引用次数: 1
Starvation-induced sleep suppression requires the Drosophila brain nutrient sensor. 饥饿引起的睡眠抑制需要果蝇的大脑营养传感器。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-03-01 DOI: 10.1080/01677063.2023.2203489
Yangkyun Oh, Greg S B Suh

Animals increase their locomotion activity and reduce sleep duration under starved conditions. This suggests that sleep and metabolic status are closely interconnected. The nutrient and hunger sensors in the Drosophila brain, including diuretic hormone 44 (DH44)-, CN-, and cupcake-expressing neurons, detect circulating glucose levels in the internal milieu, regulate the insulin and glucagon secretion and promote food consumption. Food deprivation is known to reduce sleep duration, but a potential role mediated by the nutrient and hunger sensors in regulating sleep and locomotion activity remains unclear. Here, we show that DH44 neurons are involved in regulating starvation-induced sleep suppression, but CN neurons or cupcake neurons may not be involved in regulating starvation-induced sleep suppression or baseline sleep patterns. Inactivation of DH44 neurons resulted in normal daily sleep durations and patterns under fed conditions, whereas it ablated sleep reduction under starved conditions. Inactivation of CN neurons or cupcake neurons, which were proposed to be nutrient and hunger sensors in the fly brain, did not affect sleep patterns under both fed and starved conditions. We propose that the glucose-sensing DH44 neurons play an important role in mediating starvation-induced sleep reduction.

动物在饥饿的情况下会增加运动活动,减少睡眠时间。这表明睡眠和代谢状态是密切相关的。果蝇大脑中的营养和饥饿传感器,包括利尿激素44 (DH44)-、CN-和表达纸杯蛋糕的神经元,检测内部环境中的循环葡萄糖水平,调节胰岛素和胰高血糖素的分泌,促进食物消耗。已知食物剥夺会减少睡眠时间,但营养和饥饿传感器在调节睡眠和运动活动中的潜在作用尚不清楚。在这里,我们发现DH44神经元参与调节饥饿诱导的睡眠抑制,但CN神经元或纸杯蛋糕神经元可能不参与调节饥饿诱导的睡眠抑制或基线睡眠模式。在进食条件下,DH44神经元的失活导致正常的日常睡眠时间和模式,而在饥饿条件下,它会减少睡眠。CN神经元或纸杯蛋糕神经元被认为是果蝇大脑中的营养和饥饿传感器,它们的失活在喂食和饥饿条件下都不会影响睡眠模式。我们认为葡萄糖感知DH44神经元在介导饥饿引起的睡眠减少中起重要作用。
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引用次数: 2
A deep learning analysis of Drosophila body kinematics during magnetically tethered flight. 果蝇在磁系飞行过程中身体运动学的深度学习分析。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-03-01 DOI: 10.1080/01677063.2023.2210682
Geonil Kim, JoonHu An, Subin Ha, Anmo J Kim

Flying Drosophila rely on their vision to detect visual objects and adjust their flight course. Despite their robust fixation on a dark, vertical bar, our understanding of the underlying visuomotor neural circuits remains limited, in part due to difficulties in analyzing detailed body kinematics in a sensitive behavioral assay. In this study, we observed the body kinematics of flying Drosophila using a magnetically tethered flight assay, in which flies are free to rotate around their yaw axis, enabling naturalistic visual and proprioceptive feedback. Additionally, we used deep learning-based video analyses to characterize the kinematics of multiple body parts in flying animals. By applying this pipeline of behavioral experiments and analyses, we characterized the detailed body kinematics during rapid flight turns (or saccades) in two different visual conditions: spontaneous flight saccades under static screen and bar-fixating saccades while tracking a rotating bar. We found that both types of saccades involved movements of multiple body parts and that the overall dynamics were comparable. Our study highlights the importance of sensitive behavioral assays and analysis tools for characterizing complex visual behaviors.

果蝇依靠它们的视觉来探测视觉物体并调整它们的飞行路线。尽管他们牢固地固定在一个黑暗的垂直条上,我们对潜在的视觉运动神经回路的理解仍然有限,部分原因是难以在敏感的行为分析中分析详细的身体运动学。在这项研究中,我们使用磁系飞行实验观察飞行果蝇的身体运动学,其中苍蝇可以围绕其偏航轴自由旋转,从而实现自然的视觉和本体感觉反馈。此外,我们使用基于深度学习的视频分析来表征飞行动物多个身体部位的运动学。通过应用这些行为实验和分析,我们在两种不同的视觉条件下描述了快速飞行转弯(或扫视)时的详细身体运动学:静态屏幕下的自发飞行扫视和跟踪旋转杆时注视杆的扫视。我们发现,两种类型的扫视都涉及到多个身体部位的运动,而且总体动态是相似的。我们的研究强调了敏感的行为分析和分析工具对表征复杂视觉行为的重要性。
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引用次数: 2
Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in Drosophila. 支链转氨酶活性降低可减轻果蝇夜间弱光暴露引起的代谢脆弱性。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-03-01 DOI: 10.1080/01677063.2022.2144292
Mari Kim, Gwang-Ic Son, Yun-Ho Cho, Gye-Hyeong Kim, Sung-Eun Yun, Young-Joon Kim, Jongkyeong Chung, Eunil Lee, Joong-Jean Park

The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male Drosophila. Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with the Bcat heterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when the Bcat expression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in Drosophila, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.

光在24小时内控制生物过程的节律模式被称为昼夜节律。夜间光照引起的昼夜节律紊乱会扰乱睡眠-觉醒周期,并可能导致人类心血管疾病、糖尿病、癌症和代谢紊乱。我们以雄性果蝇为研究对象,研究了暗LAN对果蝇昼夜节律和代谢的影响。夜间暴露在10勒克斯的昏暗光线下的野生型果蝇表现出24小时睡眠-觉醒行为和昼夜节律基因表达模式的改变。此外,果蝇更容易受到代谢压力的影响,比如饥饿。全身代谢物分析显示支链氨基酸(BCAAs)的数量减少,如异亮氨酸和缬氨酸。昏暗光照还增加了调节BCAAs代谢的支链氨基酸转氨酶(BCAT)和支链α-酮酸脱氢酶(BCKDC)酶复合物的表达。携带Bcat杂合突变的果蝇不容易受到饥饿应激,即使暴露在昏暗的LAN中,这些果蝇的血淋巴BCAA水平也没有下降。此外,通过条件GAL4和RNA干扰,降低成年期全身、神经元或脂肪体的Bcat表达水平,也抑制了对饥饿应激的易损性。最后,当BCAAs被喂食给暴露于LAN的野生型果蝇时,代谢脆弱性被逆转。因此,夜间短时间的昏暗光照会影响果蝇昼夜节律基因的表达和BCAA代谢,这意味着BCAA具有抑制昼夜节律紊乱引起的代谢应激的新功能。
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引用次数: 1
Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a drosophila homolog of FUS, in the brain. 谷胱甘肽s -转移酶的敲低导致cabeza在大脑中的错误定位和积累,cabeza是果蝇FUS的同源物。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2023-03-01 DOI: 10.1080/01677063.2022.2149747
Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim

Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, GstO2 knockdown in Drosophila led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. Drosophila Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after GstO2 knockdown in vivo. Downregulation of GstO2 decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of Drosophila.

谷胱甘肽s -转移酶(GSTO)是一种抗氧化酶,参与减少氧化应激。最近的研究表明,GSTOs的多态性变异影响神经退行性疾病的发病年龄和进展。虽然GSTO活性可能影响多种疾病的发展和年龄依赖性,但神经元中GSTO失活调控神经退行性疾病易感性的机制尚不清楚。在本研究中,果蝇中GstO2的敲低导致神经元中Cabeza (Caz)蛋白水平以年龄依赖的方式增加。Caz果蝇是人类FUS的同源基因,它与神经退行性疾病有关,包括肌萎缩侧索硬化症(ALS)和额颞叶痴呆(FTD)。我们发现GstO2敲除后神经元胞质Caz错定位和聚集显著增加。GstO2的下调降低了老化神经元中Caz蛋白的溶解度。这些发现表明GSTO通过调节果蝇神经系统中Caz的定位和聚集,是神经退行性疾病发展的重要调节剂。
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引用次数: 2
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Journal of neurogenetics
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