PYGL

更新于：2025-05-07

基本信息

别名

glycogen phosphorylase L、Glycogen phosphorylase, liver form、glycogen storage disease type VI

+ [5]

简介

Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.

关联

项与 PYGL 相关的药物

CP-91149

靶点

PYGL

作用机制

PYGL抑制剂

在研机构-

原研机构

Pfizer Inc.

在研适应症-

非在研适应症

2型糖尿病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PYGL 相关的临床结果

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100 项与 PYGL 相关的转化医学

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0 项与 PYGL 相关的专利（医药）

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355

项与 PYGL 相关的文献（医药）

2025-06-01·The Journal of Nutritional Biochemistry

Naringenin alleviates heat stress-induced liver injury in Ningdu yellow chickens by decreasing RIPK3 and PDC binding

Article

作者: Cai, Gaofeng ; Zheng, Zhanhong ; Liu, Zhenni ; Guo, Xiaoquan ; Qi, Qiurong ; Tang, Ruoyun ; Lin, Siting ; Liu, Ping ; Gao, Xiaona

Naringenin, a flavonoid extract, possesses anti-inflammatory, antioxidant, hepatoprotective, antitumor, and antineurotoxic properties. This study investigated the antiheat stress effects in broilers by adding 200mg/kg naringenin to the diet of Ningdu yellow chicken under heat stress conditions. Heat stress conditions was controlled at 37±2°C (7:00 a.m.-7:00 p.m.) and 24±2°C (7:00 p.m.-7:00 a.m.) at humidity maintained at 60-65%. The results suggest that naringenin elevated the body weight and the ratio of liver mass to weight of Ningdu yellow chicken significantly. Additionally, naringenin significantly reduces heat stress level, improves liver function and antioxidant capacity. Meanwhile, the levels of necroptosis indexes (CYLD, RIPK1, RIPK3 and MLKL) and oxidative stress indexes (PDC, PYGL, GLUL and GLUD1) are downregulated by naringenin. Naringenin mitigated liver damage by decreasing inflammatory indexes caused by heat stress, including NF-κB, IL-1β, IL-18 and HMGB1. This anti-inflammatory effect arose through the downlink binding of the necroptosis index (RIPK3) and the oxidative stress index (PDC) as shown in results of fluorescence co-localization and co-immunoprecipitation. The use of naringenin in poultry may be a possible feed additive to address clinical heat stress.

2025-04-01·Journal of Chromatography B

LC-HRMS profiling of Dendrobium huoshanense aqueous extract and its therapeutic effects on nonalcoholic fatty liver disease in mice through the TLR2-NF-κB and AMPK-SREBP1-SIRT1 signaling pathways

Article

作者: Ge, Xiyu ; Chen, Cunwu ; Yang, Li ; Huang, Ke ; Han, Bangxing ; Liu, Dong ; Lin, Qiyan ; Ma, Menghua ; Wang, Wei

Dendrobium huoshanense (DH) belongs to the Dendrobium genus of the Orchidaceae family and is a herbaceous plant that protects the liver and nourishes the Yin according to traditional Chinese Medicine (TCM) theory. This research aimed to determine the therapeutic effect and mechanisms of DH on a nonalcoholic fatty liver disease (NAFLD) mouse model and its chemical composition. For pharmacological research, the pathological damage and lipid accumulation in liver tissues were evaluated using HE and oil red staining, respectively. The differential proteins between the model and DHH groups were screened using 4D label-free quantitative proteomics, and the proteomic results were verified using Western blot. The potential mechanism was validated by metabolomic analysis. The main active ingredients in a DH aqueous extract were identified using UHPLC-Q Exactive HF HRMS. Pathological staining results showed that DH can reverse liver pathological damage and lipid accumulation in the NAFLD model. Quantitative proteomics revealed that the differential proteins were mainly associated with liver lipid deposition (LAL, AMPK, TM7SF2, SBCAD, and SIRT1), insulin resistance (GYS1, GYS2, PYGL, FoxO1, and PPAR-γ), and inflammation (TLR2 and MAPKAPK). Western blot verified the above-mentioned results. Metabolomic analysis also indicated that the DH aqueous extract ameliorated NAFLD in mice by affecting cholesterol metabolism and AMPK signaling pathway, proving its significant therapeutic effects on the NAFLD model. Sixty-five compounds were identified from DH aqueous extract by analyzing the precise molecular weight and MS/MS fragmentation pathway. The pharmacological mechanism of DH in treating NAFLD mainly involved the TLR2-NF-κB and AMPK-SREBP1-SIRT1 signaling pathways.

2025-04-01·Biochemical Genetics

Broadening the Phenotype and Genotype Spectrum of Glycogen Storage Disease by Unraveling Novel Variants in an Iranian Patient Cohort

Article

作者: Tehrani Fateh, Sahand ; Hashemi-Gorji, Farzad ; Miryounesi, Mohammad ; Salehpour, Shadab ; Mirfakhraie, Reza ; Norouzi Rostami, Fatemeh ; Jamshidi, Sanaz ; Ghasemi, Mohammad-Reza ; Sadeghi, Hossein ; Moghimi, Parinaz

Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2. Most types of GSDs observed in the cohort were associated with hepatomegaly, which was the most common clinical presentation. This study provides valuable insights into the phenotype and genotype spectrum of GSDs in a cohort of Iranian patients. The identification of novel variants adds to the growing body of knowledge regarding the genetic landscape of GSDs and has implications for genetic counseling and future therapeutic interventions. The diverse nature of GSDs underscores the need for comprehensive genetic testing methods to improve diagnostic accuracy. Continued research in this field will enhance our understanding of GSDs, ultimately leading to improved management and outcomes for individuals affected by these rare metabolic disorders.

项与 PYGL 相关的新闻（医药）

2023-07-18

·生物谷

J Exp Clin Cancer Res：代谢生物标记物PYGL是HNSCC的治疗靶点

头颈部鳞状细胞癌(HNSCC)是头颈部最常见的恶性肿瘤，发病率高，5年生存率差。不良的临床结果归因于患者间广泛的异质性和化疗耐药性，突显了治愈HNSCC患者的标准疗法的不足。头颈部鳞状细胞癌(HNSCC)是头颈部最常见的恶性肿瘤，发病率高，5年生存率差。不良的临床结果归因于患者间广泛的异质性和化疗耐药性，突显了治愈HNSCC患者的标准疗法的不足。因此，进一步探讨HNSCC发生的细胞机制，寻找克服化疗耐药的新靶点，对于改善HNSCC患者的预后具有重要意义。图片来源:https://doi.org/10.1186/s13046-023-02734-w 近日，来自中山大学的研究者们在J Exp Clin Cancer Res杂志上发表了题为“Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC”的文章，该研究揭示了PYGL是一种代谢相关的致癌生物标志物，通过GSH/ROS/p53通路促进HNSCC的进展、转移和化疗耐药。本研究从细胞代谢重编程的角度揭示了HNSCC的细胞层次组成，可能为未来HNSCC的治疗提供新的启示和靶点。越来越多的研究揭示了代谢重编程与肿瘤进展的关系，但代谢重编程如何影响头颈部鳞状细胞癌(HNSCC)患者间的异质性和预后仍有待进一步探索。本研究引入了一个基于代谢特性差异的细胞层次结构框架METARISK，通过使用整合了先前研究的25个原发和8个转移性HNSCC样本的单细胞参考图谱，通过去卷积重新分析了486名患者的批量转录本的细胞组成。使用机器学习方法来确定代谢相关生物标志物与预后的相关性。通过细胞功能实验和体内移植瘤小鼠模型对筛选出的基因在肿瘤进展、转移和化疗耐药中的功能进行了验证。结合细胞层次组成和临床特征，META Risk表型将多个患者队列分为两类，其中META Risk高亚组的预后不良与特定的恶性细胞簇有关，这些恶性细胞具有显著的代谢重编程活性，在转移的单细胞样本中丰富。随后针对META风险亚组之间的表型差异的分析发现，PYGL是一个关键的代谢相关生物标记物，它通过GSH/ROS/P53途径增强恶性肿瘤和化疗耐药性，导致HNSCC预后不良。机制总结图图片来源:https://doi.org/10.1186/s13046-023-02734-w 总之，本研究通过在转移样本中发现一组独特的具有高代谢活性的恶性细胞和构建META风险表型，揭示了每个患者的细胞层次结构的组成，并与不良预后相关，揭示了细胞代谢重编程是HNSCC的关键风险因素。此外，META危险表型的DEMRGs分析表明，PYGL是糖原降解的关键生物标志物，通过PYGL/GSH/ROS/P53途径指导HNSCC的发展和耐药性，从而为未来HNSCC的新的临床治疗奠定了基础。（生物谷 Bioon.com）参考文献 Jiezhong Guan et al. Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC. J Exp Clin Cancer Res. 2023 Jul 8;42(1):162. doi: 10.1186/s13046-023-02734-w.

基因疗法临床研究