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Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology 瞄准 MYC:肿瘤学中的多维调控和治疗策略
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-16 DOI: 10.1016/j.gendis.2024.101435
Yingying Duan, Zhaoshuo Liu, Qilin Wang, Junyou Zhang, Jiaxin Liu, Ziyi Zhang, Chunyan Li
MYC is dysregulated in approximately 70% of human cancers, strongly suggesting its essential function in cancer. MYC regulates many biological processes, such as cell cycle, metabolism, cellular senescence, apoptosis, angiogenesis, and immune escape. MYC plays a central role in carcinogenesis and is a key regulator of tumor development and drug resistance. Therefore, MYC is one of the most alluring therapeutic targets for developing cancer drugs. Although the search for direct inhibitors of MYC is challenging, MYC cannot simply be assumed to be undruggable. Targeting the MYC-MAX complex has been an effective method for directly targeting MYC. Alternatively, indirect targeting of MYC represents a more pragmatic therapeutic approach, mainly including inhibition of the transcriptional or translational processes of MYC, destabilization of the MYC protein, and blocking genes that are synthetically lethal with MYC overexpression. In this review, we delineate the multifaceted roles of MYC in cancer progression, highlighting a spectrum of therapeutic strategies and inhibitors for cancer therapy that target MYC, either directly or indirectly.
在大约 70% 的人类癌症中,MYC 都出现了失调,这有力地说明了它在癌症中的重要功能。MYC 调节许多生物过程,如细胞周期、新陈代谢、细胞衰老、细胞凋亡、血管生成和免疫逃逸。MYC 在致癌过程中起着核心作用,是肿瘤发生和耐药性的关键调节因子。因此,MYC 是开发抗癌药物最诱人的治疗靶点之一。虽然寻找 MYC 的直接抑制剂具有挑战性,但不能简单地认为 MYC 是不可药用的。靶向 MYC-MAX 复合物是直接靶向 MYC 的有效方法。另外,间接靶向 MYC 也是一种更实用的治疗方法,主要包括抑制 MYC 的转录或翻译过程、破坏 MYC 蛋白的稳定性以及阻断 MYC 过表达时合成致死的基因。在本综述中,我们阐述了 MYC 在癌症进展中的多方面作用,重点介绍了一系列直接或间接针对 MYC 的癌症治疗策略和抑制剂。
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引用次数: 0
Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation 重型机械力通过 Piezo1 诱导的线粒体钙下调,使牙齿矫正运动减速
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-15 DOI: 10.1016/j.gendis.2024.101434
Ye Zhu, Xuehuan Meng, Qiming Zhai, Liangjing Xin, Hao Tan, Xinyi He, Xiang Li, Guoyin Yang, Jinlin Song, Leilei Zheng
Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs), which sense biomechanical stimuli and initiate alveolar bone remodeling. Light (optimal) forces accelerate OTM, whereas heavy forces decelerate it. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces (MFs) remain unclear. This study demonstrates that mechanosensitive ion channel Piezo1-mediated Ca2+ signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs under heavy-force conditions. Heavy MF up-regulated Piezo1 in PDLCs, reducing mitochondrial Ca2+ influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM.
正畸牙齿移动(OTM)取决于牙周韧带细胞(PDLCs),它们能感知生物力学刺激并启动牙槽骨重塑。轻(最佳)力加速 OTM,而重力则使其减速。然而,PDLCs 在不同机械力(MFs)下感知生物力学刺激并影响破骨细胞活动的机制仍不清楚。本研究证明,在重力条件下,机械敏感性离子通道Piezo1介导的Ca2+信号转换是PDLCs感知和传递生物力学信号的关键。重力上调了 PDLCs 中的 Piezo1,通过抑制线粒体相关膜中 ITPR3 的表达减少了线粒体 Ca2+ 的流入。线粒体钙吸收的减少导致线粒体 DNA 胞质释放的减少,并抑制了 cGAS-STING 信号级联的激活,从而抑制了单核细胞向破骨细胞的分化。在重型 MF 条件下抑制 Piezo1 或上调 STING 的表达可显著增加破骨细胞的活性并加速 OTM。这些发现表明,重型 MF 诱导的 Piezo1 在 PDLCs 中的表达与 OTM 过程中破骨细胞活性的控制密切相关,并在牙槽骨重塑过程中发挥着重要作用。这一机制可能是加速 OTM 的潜在治疗靶点。
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引用次数: 0
MAFB-mediated CEBPA regulated human urothelium growth through Wnt/β-catenin signaling pathway MAFB 介导的 CEBPA 通过 Wnt/β-catenin 信号通路调控人尿路细胞的生长
IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-13 DOI: 10.1016/j.gendis.2024.101432
Zhenmin Liu , Xingguo Luo , Zhicheng Zhang , Qiang Zhang , Chong Wang , Hongsong Chen , Chunlan Long , Xing Liu , Guanghui Wei
MAFB is essential for regulating male-type urethral differentiation, and especially, its variation can contribute to hypospadias in mice. However, the potential mechanism is still unclear. Here we observed that the basic leucine zipper (bZIP) transcription factor MAFB and CCAAT/enhancer-binding protein alpha (CEBPA) could promote human urothelium SV-HUC-1 growth. Moreover, MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients. Based on transcriptome sequencing analysis and Western blot, MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells. Meanwhile, we observed blocked cell-cycle progression from the G1 to the S phase, inhibited cell proliferation, and activated apoptosis. Furthermore, MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium. The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA. Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.
MAFB对于调节雄性尿道分化至关重要,尤其是其变异可导致小鼠尿道下裂。然而,其潜在机制仍不清楚。在这里,我们观察到碱性亮氨酸拉链(bZIP)转录因子MAFB和CCAAT/增强子结合蛋白α(CEBPA)能促进人尿道上皮细胞SV-HUC-1的生长。此外,MAFB和CEBPA在尿道下裂患者包皮组织中的表达量减少。基于转录组测序分析和Western印迹,我们发现MAFB敲除可抑制CEBPA蛋白的表达,并抑制Wnt/β-catenin信号在尿道细胞中的传递。同时,我们观察到MAFB阻滞了细胞周期从G1期到S期的进展,抑制了细胞增殖并激活了细胞凋亡。此外,MAFB 还能促进 CEBPA 的转录,调控尿路细胞的增殖。上述结果表明,MAFB通过下调CEBPA抑制Wnt/β-catenin信号通路,从而抑制了尿路上皮SV-HUC-1的生长。我们的研究结果为了解尿道下裂相关基因及其致病机制提供了新的视角。
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引用次数: 0
HMGN2 accelerates the proliferation and cell cycle progression of glioblastoma by regulating CDC20 expression HMGN2 通过调控 CDC20 的表达加速胶质母细胞瘤的增殖和细胞周期进程
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-12 DOI: 10.1016/j.gendis.2024.101433
Jiacheng Zhong, Shuang Shi, Wen Peng, Hongjuan Cui, Xiaochuan Sun
Gliomas represent the most common primary malignant intracranial tumors in adults. Despite recent advances in treatment, the prognosis of patients with glioblastoma remains poor. Epigenetic abnormalities, the hallmarks of various types of cancer, contribute to the dysregulated expression of cancer-related genes. Post-translational modification of histones plays a pivotal role in cancer development and progression by modulating gene transcription, chromatin remodeling, and nuclear structure. Therefore, further exploration of the molecular mechanisms of epigenetic regulation in gliomas and the identification of superior therapeutic targets are required. High-mobility group nucleosomal-binding domain 2 (HMGN2) participates in the epigenetic regulation of genes through histone modification and exhibits significant differential expression between glioma and normal tissues. However, the effect of HMGN2 on gliomas and its underlying mechanisms remain unclear. This study aimed to elucidate these uncertainties by demonstrating that HMGN2 significantly promotes the proliferation of glioma cells. HMGN2 binds to histones and promotes the stability of H3K27ac acetylation in the cell division cycle 20 (CDC20) promoter region, enhancing the transcriptional activity of CDC20 and increasing the proliferation of glioma cells. Moreover, we found that CDC20 expression was negatively correlated with the survival time of patients with glioma. These results suggest that targeting epigenetic regulation, such as the HMGN2/CDC20 axis, may provide a novel direction for the treatment of gliomas.
胶质瘤是成人最常见的原发性颅内恶性肿瘤。尽管最近在治疗方面取得了进展,但胶质母细胞瘤患者的预后仍然很差。表观遗传异常是各种癌症的标志,它导致癌症相关基因表达失调。组蛋白的翻译后修饰通过调节基因转录、染色质重塑和核结构,在癌症的发生和发展过程中起着举足轻重的作用。因此,需要进一步探索胶质瘤中表观遗传调控的分子机制,并确定优良的治疗靶点。高迁移率基团核糖体结合域 2(HMGN2)通过组蛋白修饰参与基因的表观遗传调控,并在胶质瘤和正常组织之间表现出显著的表达差异。然而,HMGN2 对胶质瘤的影响及其内在机制仍不清楚。本研究旨在通过证明 HMGN2 能显著促进胶质瘤细胞的增殖来阐明这些不确定性。HMGN2与组蛋白结合,促进细胞分裂周期20(CDC20)启动子区H3K27ac乙酰化的稳定性,增强CDC20的转录活性,增加胶质瘤细胞的增殖。此外,我们还发现 CDC20 的表达与胶质瘤患者的生存时间呈负相关。这些结果表明,以HMGN2/CDC20轴等表观遗传调控为靶点,可能为胶质瘤的治疗提供一个新的方向。
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引用次数: 0
Systematic pan-cancer analysis identifies DNASE2 as a potential prognostic marker and immunotherapeutic target for glioblastoma multiforme 系统性泛癌分析确定 DNASE2 是多形性胶质母细胞瘤的潜在预后标记和免疫治疗靶点
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.1016/j.gendis.2024.101431
Jun Cao, Si Chen, Ping An, Xingqiang Wang, Xinru Xiao, Shichao Li, Ye Cheng
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引用次数: 0
Oncogenic activation of PI3KCA in cancers: Emerging targeted therapies in precision oncology 癌症中 PI3KCA 的致癌激活:精准肿瘤学中的新兴靶向疗法
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.1016/j.gendis.2024.101430
Yuxiang Wang, Valery Rozen, Yiqing Zhao, Zhenghe Wang
Phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of a p110 catalytic subunit and a p85 regulatory subunit. The PIK3CA gene, which encodes the p110α, is the most frequently mutated oncogene in cancer. Oncogenic PIK3CA mutations activate the PI3K pathway, promote tumor initiation and development, and mediate resistance to anti-tumor treatments, making the mutant p110α an excellent target for cancer therapy. PIK3CA mutations occur in two hotspot regions: one in the helical domain and the other in the kinase domain. The PIK3CA helical and kinase domain mutations exert their oncogenic function through distinct mechanisms. For example, helical domain mutations of p110α gained direct interaction with insulin receptor substrate 1 (IRS-1) to activate the downstream signaling pathways. Moreover, p85β proteins disassociate from helical domain mutant p110α, translocate into the nucleus, and stabilize enhancer of zeste homolog 1/2 (EZH1/2). Due to the fundamental role of PI3Kα in tumor initiation and development, PI3Kα-specific inhibitors, represented by FDA-approved alpelisib, have developed rapidly in recent decades. However, side effects, including on-target side effects such as hyperglycemia, restrict the maximum dose and thus clinical efficacy of alpelisib. Therefore, developing p110α mutant-specific inhibitors to circumvent on-target side effects becomes a new direction for targeting PIK3CA mutant cancers. In this review, we briefly introduce the function of the PI3K pathway and discuss how PIK3CA mutations rewire cell signaling, metabolism, and tumor microenvironment, as well as therapeutic strategies under development to treat patients with tumors harboring a PIK3CA mutation.
磷酸肌醇 3 激酶(PI3K)是由 p110 催化亚基和 p85 调节亚基组成的异源二聚体。编码 p110α 的 PIK3CA 基因是癌症中最常发生突变的癌基因。致癌的 PIK3CA 基因突变会激活 PI3K 通路,促进肿瘤的发生和发展,并介导对抗肿瘤治疗的耐药性,从而使突变的 p110α 成为癌症治疗的绝佳靶点。PIK3CA 突变发生在两个热点区域:一个在螺旋结构域,另一个在激酶结构域。PIK3CA 螺旋结构域和激酶结构域突变通过不同的机制发挥致癌功能。例如,螺旋结构域突变的 p110α 可与胰岛素受体底物 1(IRS-1)直接相互作用,激活下游信号通路。此外,p85β蛋白与螺旋结构域突变的p110α脱离,转运到细胞核,并稳定泽斯特同源增强子1/2(EZH1/2)。由于 PI3Kα 在肿瘤发生和发展中的基础性作用,近几十年来,以美国 FDA 批准的 alpelisib 为代表的 PI3Kα 特异性抑制剂发展迅速。然而,包括高血糖等靶向副作用在内的副作用限制了阿来替尼的最大剂量,从而限制了其临床疗效。因此,开发 p110α 突变特异性抑制剂以规避靶向副作用成为靶向 PIK3CA 突变癌症的新方向。在这篇综述中,我们简要介绍了PI3K通路的功能,讨论了PIK3CA突变如何重新连接细胞信号传导、新陈代谢和肿瘤微环境,以及正在开发的治疗PIK3CA突变肿瘤患者的策略。
{"title":"Oncogenic activation of PI3KCA in cancers: Emerging targeted therapies in precision oncology","authors":"Yuxiang Wang, Valery Rozen, Yiqing Zhao, Zhenghe Wang","doi":"10.1016/j.gendis.2024.101430","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101430","url":null,"abstract":"Phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of a p110 catalytic subunit and a p85 regulatory subunit. The <ce:italic>PIK3CA</ce:italic> gene, which encodes the p110α, is the most frequently mutated oncogene in cancer. Oncogenic <ce:italic>PIK3CA</ce:italic> mutations activate the PI3K pathway, promote tumor initiation and development, and mediate resistance to anti-tumor treatments, making the mutant p110α an excellent target for cancer therapy. <ce:italic>PIK3CA</ce:italic> mutations occur in two hotspot regions: one in the helical domain and the other in the kinase domain. The <ce:italic>PIK3CA</ce:italic> helical and kinase domain mutations exert their oncogenic function through distinct mechanisms. For example, helical domain mutations of p110α gained direct interaction with insulin receptor substrate 1 (IRS-1) to activate the downstream signaling pathways. Moreover, p85β proteins disassociate from helical domain mutant p110α, translocate into the nucleus, and stabilize enhancer of zeste homolog 1/2 (EZH1/2). Due to the fundamental role of PI3Kα in tumor initiation and development, PI3Kα-specific inhibitors, represented by FDA-approved alpelisib, have developed rapidly in recent decades. However, side effects, including on-target side effects such as hyperglycemia, restrict the maximum dose and thus clinical efficacy of alpelisib. Therefore, developing p110α mutant-specific inhibitors to circumvent on-target side effects becomes a new direction for targeting <ce:italic>PIK3CA</ce:italic> mutant cancers. In this review, we briefly introduce the function of the PI3K pathway and discuss how <ce:italic>PIK3CA</ce:italic> mutations rewire cell signaling, metabolism, and tumor microenvironment, as well as therapeutic strategies under development to treat patients with tumors harboring a <ce:italic>PIK3CA</ce:italic> mutation.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arhgap29 deficiency causes EEC like syndrome in mice Arhgap29 缺乏会导致小鼠 EEC 样综合征
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101404
Dandan Chi, Yumeng Wang, Lili Yu, Wenyan Ruan, Beibei Zhang, Jian Ma, Xiaohong Duan, Yongqing Huang
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引用次数: 0
Triplet therapy overcomes 3rd-EGFR TKI-resistant EGFR-L858R/T790M/C797S in trans and in cis/L718Q mutation 三联疗法可克服第三代表皮生长因子受体TKI耐药的表皮生长因子受体-L858R/T790M/C797S反式和顺式/L718Q突变
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101408
Kaibo Ding, Zhongsheng Peng, Yanjun Xu
{"title":"Triplet therapy overcomes 3rd-EGFR TKI-resistant EGFR-L858R/T790M/C797S in trans and in cis/L718Q mutation","authors":"Kaibo Ding, Zhongsheng Peng, Yanjun Xu","doi":"10.1016/j.gendis.2024.101408","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101408","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease TFE3 介导的神经保护:清除AAV-α-突触核蛋白帕金森病模型中聚集的α-突触核蛋白和积累的线粒体
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101429
Xin He, Mulan Chen, Yepeng Fan, Bin Wu, Zhifang Dong
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions containing aggregated α-synuclein (α-Syn). While the pathology of PD is multifaceted, the aggregation of α-Syn and mitochondrial dysfunction are well-established hallmarks in its pathogenesis. Recently, TFE3, a transcription factor, has emerged as a regulator of autophagy and metabolic processes. However, it remains unclear whether TFE3 can facilitate the degradation of α-Syn and regulate mitochondrial metabolism specifically in dopaminergic neurons. In this study, we demonstrate that TFE3 overexpression significantly mitigates the loss of dopaminergic neurons and reduces the decline in tyrosine hydroxylase-positive fiber density, thereby restoring motor function in an α-Syn overexpression model of PD. Mechanistically, TFE3 overexpression reversed α-Syn-mediated impairment of autophagy, leading to enhanced α-Syn degradation and reduced aggregation. Additionally, TFE3 overexpression inhibited α-Syn propagation. TFE3 overexpression also reversed the down-regulation of Parkin, promoting the clearance of accumulated mitochondria, and restored the expression of PGC1-α and TFAM, thereby enhancing mitochondrial biogenesis in the adeno-associated virus-α-Syn model. These findings further underscore the neuroprotective role of TFE3 in PD and provide insights into its underlying mechanisms, suggesting TFE3 as a potential therapeutic target for PD.
帕金森病(Parkinson's disease,PD)是一种神经退行性疾病,其特征是神经元内含有聚集的α-突触核蛋白(α-Syn)的纤维包裹体。虽然帕金森病的病理是多方面的,但α-Syn的聚集和线粒体功能障碍是其发病机制中公认的标志。最近,转录因子 TFE3 成为自噬和代谢过程的调节因子。然而,TFE3是否能促进α-Syn的降解并调节多巴胺能神经元的线粒体代谢仍不清楚。在本研究中,我们证明了在α-Syn过表达的帕金森病模型中,TFE3的过表达能显著缓解多巴胺能神经元的丢失,并减少酪氨酸羟化酶阳性纤维密度的下降,从而恢复运动功能。从机理上讲,TFE3的过表达逆转了α-Syn介导的自噬损伤,导致α-Syn降解增强、聚集减少。此外,TFE3 的过表达抑制了 α-Syn 的传播。TFE3 的过量表达还逆转了 Parkin 的下调,促进了累积线粒体的清除,并恢复了 PGC1-α 和 TFAM 的表达,从而增强了腺相关病毒-α-Syn 模型中线粒体的生物生成。这些研究结果进一步强调了TFE3在帕金森病中的神经保护作用,并深入揭示了其潜在机制,提示TFE3是帕金森病的潜在治疗靶点。
{"title":"TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease","authors":"Xin He, Mulan Chen, Yepeng Fan, Bin Wu, Zhifang Dong","doi":"10.1016/j.gendis.2024.101429","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101429","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions containing aggregated α-synuclein (α-Syn). While the pathology of PD is multifaceted, the aggregation of α-Syn and mitochondrial dysfunction are well-established hallmarks in its pathogenesis. Recently, TFE3, a transcription factor, has emerged as a regulator of autophagy and metabolic processes. However, it remains unclear whether TFE3 can facilitate the degradation of α-Syn and regulate mitochondrial metabolism specifically in dopaminergic neurons. In this study, we demonstrate that TFE3 overexpression significantly mitigates the loss of dopaminergic neurons and reduces the decline in tyrosine hydroxylase-positive fiber density, thereby restoring motor function in an α-Syn overexpression model of PD. Mechanistically, TFE3 overexpression reversed α-Syn-mediated impairment of autophagy, leading to enhanced α-Syn degradation and reduced aggregation. Additionally, TFE3 overexpression inhibited α-Syn propagation. TFE3 overexpression also reversed the down-regulation of Parkin, promoting the clearance of accumulated mitochondria, and restored the expression of PGC1-α and TFAM, thereby enhancing mitochondrial biogenesis in the adeno-associated virus-α-Syn model. These findings further underscore the neuroprotective role of TFE3 in PD and provide insights into its underlying mechanisms, suggesting TFE3 as a potential therapeutic target for PD.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic significance and multidimensional roles of interferon regulatory factors in cancer biology: A comprehensive analysis 干扰素调节因子在癌症生物学中的预后意义和多维作用:综合分析
IF 6.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.1016/j.gendis.2024.101426
Guo Ji, Shuyuan Xian, Jiaqi Song, Shiyu Mao, Man Pi, Qiongyi Huang, Xue Han, Jian Yin, Zan Wu, Runzhi Huang, Dongyan Han, Zhengyan Chang
{"title":"Prognostic significance and multidimensional roles of interferon regulatory factors in cancer biology: A comprehensive analysis","authors":"Guo Ji, Shuyuan Xian, Jiaqi Song, Shiyu Mao, Man Pi, Qiongyi Huang, Xue Han, Jian Yin, Zan Wu, Runzhi Huang, Dongyan Han, Zhengyan Chang","doi":"10.1016/j.gendis.2024.101426","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101426","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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