更新于：2024-11-01

PGC-1α

更新于：2024-11-01

基本信息

别名

GC-1-alpha、LEM6、Ligand effect modulator 6

+ [10]

简介

Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:10713165, PubMed:20005308, PubMed:21376232). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:10713165, PubMed:20005308, PubMed:21376232). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:10713165, PubMed:20005308, PubMed:21376232). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:16753578, PubMed:23142079). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (PubMed:23836911). Also involved in the integration of the circadian rhythms and energy metabolism (By similarity). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity).

关联

项与 PGC-1α 相关的药物

Medioresinol

靶点

PGC-1α

作用机制

PGC-1α agonists

在研机构

中国药科大学

原研机构

中国药科大学

在研适应症

缺血性卒中

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TQS-168

靶点

PGC-1α

作用机制

PGC-1α调节剂

在研机构

Tranquis Therapeutics, Inc.初创企业

原研机构

Tranquis Therapeutics, Inc.初创企业

在研适应症

肌萎缩侧索硬化 [+4]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

ZLN005

靶点

PGC-1α

作用机制

PGC-1α调节剂

在研机构

中国科学院上海药物研究所

原研机构

中国科学院上海药物研究所

在研适应症

2型糖尿病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 PGC-1α 相关的临床试验

CTIS2023-504746-54-00 / Not yet recruiting

- TQS-168-ALS-101

开始日期-

申办/合作机构

Tranquis Therapeutics, Inc.初创企业

ISRCTN46651459 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single-and Multiple-, Ascending-Dose Study of the Safety, Tolerability and Pharmacokinetics of TQS-168 in Healthy Male Adults

开始日期2021-06-09

申办/合作机构

Tranquis Therapeutics, Inc.初创企业

100 项与 PGC-1α 相关的临床结果

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100 项与 PGC-1α 相关的转化医学

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0 项与 PGC-1α 相关的专利（医药）

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7,912

项与 PGC-1α 相关的文献（医药）

2025-01-01·Gene

Exploring the effects of naringenin on cell functioning and energy synthesis in the hippocampus of male Wistar rats with chronic tinnitus, by examining genetic indicators such as Bax, Bcl-2, Tfam, and Pgc-1α

Article

作者: Nasehi, Mohammad ; Zarrindast, Mohammad-Reza ; Safavi-Naeini, Seyede-Mojdeh ; Safavi-Naeini, Seyed-Abbas

BACKGROUNDThe pivotal factors, including neural plasticity, oxidative stress, neuronal inflammation, and apoptosis, play a significant role in the pathogenesis of tinnitus. The balance between Bax/Bcl-2 genes is an important factor in determining the rate of apoptosis. Pgc-1α and Tfam genes are fundamental regulators of mitochondrial biogenesis. Naringenin possesses significant antioxidant, neuroprotective, anti-inflammatory, anti-apoptotic, and antiviral properties, and its compounds are effective on cell signaling pathways.AIMSIn light of the aforementioned information, we endeavored to evaluate the impact of naringenin on the expression levels of Bax, Bcl-2, Pgc-1α, and Tfam genes in the hippocampus of male Wistar rats with chronic tinnitus.MATERIAL AND METHODSTo demonstrate the existence of tinnitus, all rats were instructed to complete an "active avoidance test" utilizing a conditioning box. The expression levels of genes mentioned above were assessed using real-time PCR.RESULTSThe sodium salicylate at a dosage of 350 mg/kg showed an upregulation in the expression level of Bax and a downregulation in the expression level of the Bcl-2 gene (p < 0.001). Furthermore, the sodium salicylate displayed significantly higher expression levels of Tfam and Pgc-1α (p < 0.001) genes. The naringenin, at a dose of 100 mg/kg, led to a decrease in Bax gene expression (p < 0.05) and an increase in Bcl-2 gene expression (p < 0.05). On the other hand, naringenin restored the expression level of both Tfam (p < 0.001) and Pgc-1α (p < 0.01) genes.CONCLUSIONSOur research findings demonstrate that sodium salicylate-induced tinnitus leads to enhanced apoptosis and mitochondrial biogenesis within the hippocampus. Additionally, our evidence recommends that naringenin can reduce apoptosis effectively and maintain a balanced mitochondrial state.

2025-01-01·Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology

Up-regulated mitochondrial biogenesis associated with GH/IGF axis in the ovaries of muskrats (Ondatra zibethicus)

Article

作者: Ramírez, María Daniela Artigas ; Zhang, Haolin ; Yuan, Zhengrong ; Han, Yingying ; Liu, Yuning ; Weng, Qiang ; Lu, Wenjing ; Chen, Yuan

Mitochondria play a critical role in follicular development and ovulation, at least in part through the actions of growth hormone (GH)/insulin-like growth factor-1 (IGF-1) on mitochondrial biogenesis. This study aimed to identify seasonal alterations in the GH/IGF-1 system and mitochondrial biogenesis in muskrat (Ondatra zibethicus) ovaries. We utilized the muskrat, a typical seasonal breeder, to clarify the potential impact of the GH/IGF-1 system on mitochondrial biogenesis across different breeding seasons using immunohistochemistry, gene expression and high-throughput sequencing. Alterations in follicular development existed in muskrat ovaries between the breeding season (BS) and non-breeding season (NBS), accompanied by a striking decrease in circulating and ovarian GH and IGF-1 concentrations. GH, GHR, IGF-1, IGF-1R, and mitochondrial biogenesis markers were localized in the ovarian cells of muskrats during both seasons. In contrast, Gh, Ghr, Igf-1, Igf-1r, Ppargc1a, Ppargc1b, Tfam, and Nrf1/2 mRNA levels were higher in BS. The relative levels of GH and IGF-1 in circulation and ovaries were positively associated with mitochondrial biogenesis markers. Additionally, RNA-seq analysis demonstrated that differentially expressed genes might be associated with insulin and PI3K/Akt signaling pathways, as well as mitochondrial function-related pathways. These findings suggest that the intra-ovarian GH/IGF-1 system, which is associated with seasonal changes in mitochondrial biogenesis, is activated in muskrat ovaries in BS.

2025-01-01·Journal of Ethnopharmacology

Study on the role of Dihuang Yinzi in regulating the AMPK/SIRT1/PGC-1α pathway to promote mitochondrial biogenesis and improve Alzheimer's disease

Article

作者: He, Wenbin ; Han, Cheng ; Li, Qinqing ; Zhang, Zheng ; Hou, Jiangqi ; Zhang, Junlong ; Du, Yuzhong ; Zhu, Yousong ; Zhao, Qiong ; Qin, Yali ; Zhu, Chao

ETHNOPHARMACOLOGICAL RELEVANCEDihuang Yinzi (DHYZ) is a classic prescription in traditional Chinese medicine. Its therapeutic effect on Alzheimer's disease (AD) has been widely validated. However, the underlying molecular mechanisms of DHYZ in AD treatment remain unclear and require further research.AIM OF THE STUDYElucidating DHYZ's promotion of mitochondrial biogenesis through the AMPK/SIRT1/PGC-1α pathway improves neuronal loss, mitochondrial damage, and memory deficits in AD.MATERIALS AND METHODSAdministering DHYZ by gavage to SAMP8 mice, after completing behavioral tests, the effects of DHYZ on hippocampal neuron loss and mitochondrial structural damage in AD model mice were assessed using Nissl staining and transmission electron microscopy. Western blot was used to detect the expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, mitochondrial fusion protein MFN2, and mitochondrial fission proteins DRP1 and FIS1. At the same time, immunofluorescence (IF) was employed to measure the relative fluorescence intensity of mitochondrial fusion protein MFN1. After determining the optimal dose of DYHZ for treating AD, we conducted mechanistic studies. By intraperitoneally injecting SAMP8 mice with the AMPK inhibitor (Compound C) to inhibit AMPK protein expression and subsequently treating them with DHYZ, the impact of DHYZ on hippocampal neurons in AD model mice was evaluated using Nissl and hematoxylin-eosin staining. Western blot was used to detect the protein expression of AMPK, p-AMPK, SIRT1, PGC-1α, NRF1, and TFAM. In contrast, IF was used to measure the relative fluorescence intensity of PGC-1α, NRF1, and TFAM proteins in the hippocampal CA1 region.RESULTSDHYZ significantly improved AD model mice's cognitive impairment and memory deficits and mitigated hippocampal neuron loss and degeneration. Additionally, it ameliorated mitochondrial morphological structures. DHYZ upregulated the protein expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, and mitochondrial fusion proteins MFN1 and MFN2 while inhibiting the expression of mitochondrial fission proteins DRP1 and FIS1. Further studies revealed that DHYZ could upregulate the expression of the AMPK/SIRT1/PGC-1α pathway proteins and their downstream proteins NRF1 and TFAM.CONCLUSIONDHYZ promotes mitochondrial biogenesis by activating the AMPK/SIRT1/PGC-1α signaling pathway, thereby improving memory deficits, neuronal loss, and mitochondrial dysfunction in AD.

项与 PGC-1α 相关的新闻（医药）

2024-10-22

·BioSpace

SOTIO Announces Upcoming Poster Presentations at the 2024 SITC Annual Meeting

PRAGUE & BASEL, Switzerland & BOSTON--(BUSINESS WIRE)-- SOTIO Biotech , a clinical-stage immuno-oncology company owned by PPF Group, today announced it will present three posters at the 2024 Society for Immunotherapy of Cancer Meeting taking place November 6 - 10, 2024, in Houston, TX. Data to be presented include the investigation of a novel chimeric PGC-1α transgene to enhance CAR T cell efficacy in patients with solid tumors. The VICTORIA-01 study is currently evaluating the safety, tolerability and initial efficacy of SOT201 monotherapy for the treatment of advanced solid tumors, as well as data around SOT201, a next-generation clinical stage PD-1-targeting immunocytokine. Poster details are as follows: Title: “Chimeric PGC-1α expression in CAR-T cells improves metabolic function and anti-tumor efficacy in solid tumors” Abstract Number: 273 Date: Thursday, November 7 and Friday, November 8, 2024 Presenting Author: Amy Jensen-Smith Title: “VICTORIA-01: A multicenter, open-label, phase 1 study to evaluate the safety and preliminary efficacy of SOT201 in patients with advanced or metastatic solid tumors” Abstract Number: 675 Date: Friday, November 8, 2024 Presenting Author: Aung Naing Title: “SOT201, a novel cis-acting PD-1/IL-15 mutein-based immunocytokine that reinvigorates anti-tumor immunity qualitatively superior to PD-1/IL-2v-based IL-2/15Rβγ agonism” Abstract Number: 940 Date: Saturday, November 9, 2024 Presenting Author: Irena Adkins Presentation materials will be available after presentations conclude here . About SOTIO Biotech SOTIO Biotech (SOTIO) is shaping the future of targeted cancer therapies by translating compelling science into patient benefit. The SOTIO pipeline includes three clinical-stage programs: SOT102, a next-generation Claudin-18.2-targeted antibody-drug conjugate; BOXR1030, a metabolically-enhanced CAR-T cell therapy targeting GPC3-expressing tumors; and SOT201, a next-generation PD-1-targeting immunocytokine. SOTIO is a member of the PPF Group. For more information, please visit the company’s website at . SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries. Contacts Company contact: Richard Kapsa Head of Communication T: (+420) 224 174 448 M: (+420) 603 280 971 kapsa@sotio.com Media contact: Lisa Raffensperger Ten Bridge Communications M: +1 (617) 903-8783 lisa@tenbridgecommunications.com

免疫疗法临床1期细胞疗法AACR会议

2024-08-12

·生物谷

Science子刊：一种称为SR-18292 的小分子有望治疗镰状细胞病

研究表明，将一种小分子与羟基脲结合使用，可以通过不同的机制提高胎儿血红蛋白的生成。这可能为那些对羟基脲单独治疗效果不佳的镰状细胞病患者提供一种重要的新治疗选择。镰状细胞病虽然罕见，但却是最常见的遗传性血液疾病。根据美国疾病控制预防中心（CDC）的数据，美国有超过 10 万人患有这种疾病，其中 90% 以上是黑人。尽管一种名为羟基脲（hydroxyurea）的药物可以减轻疼痛并减少住院次数，但并非所有成年人都对这种治疗方法反应良好。在一项新的研究中，来自波士顿大学波士顿医学中心的研究人员发现了一种新的小分子，可以减少镰状红细胞并改善症状。这一发现为开发更有效的疗法提供了概念验证。相关研究结果发表在2024年8月2日的Science Advances期刊上，论文标题为“PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease”。论文通讯作者、波士顿医学中心镰状细胞病卓越研究中心研究员 Shuaiying Cui 博士说，“我们发现了一种很有希望的方法，可以为传统治疗方法无效的镰状细胞病患者带来希望。” 镰状细胞病患者的红细胞会变成“镰状”或新月形，这是因为一种基因突变影响血红蛋白的功能，而血红蛋白是将氧气从肺部输送到其他组织的蛋白。这种突变会使血红蛋白分子粘在一起，阻碍血液流动，导致患者剧痛发作。然而，胎儿血红蛋白（人们通常在出生后就停止制造）可以减少镰状红细胞的数量。羟基脲通过提高胎儿血红蛋白发挥作用，但会导致毒副作用，而且并非对所有人都有帮助。在这项研究中，研究者测试了一种靶向PGC-1 α蛋白的小分子对胎儿血红蛋白生成和镰状红细胞的影响，其中PGC-1 α是一种在脂肪组织中发现的蛋白，在红细胞的成熟和存活中起作用。他们发现这种称为SR-18292的小分子能增加人类造血干细胞中的胎儿血红蛋白生成，并减少镰状细胞病小鼠体内畸形红细胞的数量。这表明SR-18292本身就能改善镰状细胞病的病理。不过，当与羟基脲联合使用时，SR-18292 对胎儿血红蛋白的生成产生了更大的影响。 Cui说，“我们的研究表明，将一种小分子与羟基脲结合使用，可以通过不同的机制提高胎儿血红蛋白的生成。这可能为那些对羟基脲单独治疗效果不佳的镰状细胞病患者提供一种重要的新治疗选择。” 图片来自Science Advances, 2024, doi:10.1126/sciadv.adn8750 为了确定SR-18292是否会影响控制胎儿血红蛋白生成的基因，研究者对接受该分子处理的人类造血干细胞进行了单细胞RNA测序。他们发现，许多基因在接受SR-18292处理后表达不同，其中包括BCL11A的下调，其中BCL11A通常抑制胎儿血红蛋白的产生，是第一种CRISPR基因编辑疗法治疗镰状细胞病的靶基因。美国食品药品管理局（FDA）最近批准了治疗镰状细胞病的疗法，波士顿医学中心正在为患者提供这些疗法，但这些疗法成本高昂，而且由于程序复杂，还不能在全球范围内推广治疗。Cui希望这项新的研究是为治疗资源匮乏的社区的患者开发一种治疗方法的第一步。 Cui 说，“这一突破标志着波士顿医学中心在为所有患者寻求更有效的镰状细胞病治疗方法的道路上迈出了重要一步。有朝一日，我们希望我们的药物能应用于全球各地可能无法获得现有基因疗法的镰状细胞病患者。”（生物谷Bioon.com）参考资料： Yanan Sun et al. PGC-1α Agonism Induces Fetal Hemoglobin and Exerts Anti-Sickling Effects in Sickle Cell Disease. Science Advances, 2024, doi:10.1126/sciadv.adn8750.

临床1期

2024-06-15

·生物探索

Cell Stem Cell | 自噬可以恢复衰老造血干细胞的代谢失调和再生能力

引言自噬对于寿命调控通路十分关键，并且自噬也在造血干细胞（HSC）响应营养胁迫过程中起重要作用，随着衰老，HSC的再生潜力下降，而一部分HSC的自噬流增加并保持再生能力，但是激活自噬的信号以及维持这些自噬激活的衰老的HSC功能的机制仍不清楚。近日，来自美国哥伦比亚大学的Emmanuelle Passegue研究团队在Cell Stem Cell上发表题为Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells的文章，发现在衰老的小鼠HSC中，自噬可以代偿慢性炎症诱导的代谢失调，并且对于自噬的短暂调控可以恢复衰老HSC的糖酵解状态和再生能力。为了研究衰老的HSC（oHSC）中自噬激活和未激活之间的差异，研究人员使用24个月大的Gfp-Lc3自噬报告子小鼠进行研究，他们分离了自噬激活（AThi）的oHSC和未激活（ATlo）的oHSC，也用2个月大的小鼠分离了年轻的HSC（yHSC）作为对照，通过ATAC-seq，他们发现yHSC和oHSC的染色体可及性之间存在着很大差异，oHSC的开放位点显著增加，但是在两种oHSC亚型之间则没有显著差异，于是他们猜测这两种oHSC亚型之间的差异可能是环境介导的，并且与细胞状态和激活水平相关。接下来他们对这两种亚型进行了仔细的转录组分析，发现在AThi的oHSC中，炎症信号通路相关基因显著富集，而在ATlo的oHSC中，氧化磷酸化通路相关基因显著富集，并且AThi oHSC细胞几乎全部处于G0/G1期。为了研究在HSC中促炎症信号是否可以直接激活自噬，他们给年轻的Gfp-Lc3报告子小鼠注射IFN-γ或TNF-α，发现在yHSC中，急性炎症可以瞬时激活自噬，而慢性炎症可以促进自噬升高保护HSC功能。为了研究慢性炎症对HSC功能的代谢影响，他们检测了cIL1刺激的yHSC和oHSC的营养感知信号通路PI3K/AKT/FoxO的状态，发现在衰老的HSC中AKT信号通路被抑制，葡萄糖代谢和摄入下降，葡萄糖转运子Glut1的细胞表面表达也降低。在yHSC和oHSC之间差异表达最大的基因以及在炎症激活的AThi oHSC和yHSC中上调最明显的基因之一是Socs3，这是一个已知的炎症调控因子和JAK/STAT和胰岛素/IGF-1信号通路的抑制因子，他们构建了一个Socs3fl/fl:Mx1-Cre (Soc3cKO)小鼠来条件性敲除HSC中的Socs3，注射poly(IC)来诱导条件性敲除，同时注射促炎症细胞因子，发现在Soc3cKO小鼠中会诱导致死效应，并且是Socs3的上调介导了炎症导致的代谢变化。接下来他们想知道自噬的参与如何代偿oHSC中受损的糖酵解，RNA-seq结果分析发现许多与营养代谢相关的代谢酶的表达上调，包括脂肪酸氧化和谷氨酰胺摄入，其中在AThi和ATlo oHSC之间差异最大的基因之一是Ppargc1a，该基因编码线粒体生物合成和能量代谢的调控因子PGC-1α。通过对yHSC、AThi和ATlo oHSC进行代谢组分析发现，在AThi oHSC中脂肪酸代谢通路活性上调，可能可以部分替代糖酵解代谢来维持HSC功能。最后他们想知道是否可以通过操纵自噬来恢复oHSC的糖酵解代谢和再生功能，发现24小时的禁食/再进食可以恢复oHSC的再生能力。自噬可以拮抗衰老HSC中炎症导致的糖酵解抑制（Credit: Cell Stem Cell）总的来说，这项研究发现衰老的HSC中不同的自噬状态是环境介导的，慢性炎症诱导的糖酵解抑制可以激活自噬，Socs3介导了衰老HSC中的代谢失调和自噬适应，禁食-再进食可以恢复衰老HSC的糖酵解状态和再生能力，为将来利用调控自噬来使造血系统年轻化提供了基础。原文链接 https://doi.org/10.1016/j.stem.2024.04.020 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

放射疗法