作为GFRAL连接体的GDF15类似物
Andrea Di Santo1, Livio Tarchi2, Gianluca Villa3
1Department of Neuroscience, Psychology, Pharmacology and Infant Health, Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, University of, Florence, Via Ugo Schiff, 6, Sesto Fiorentino, FI, 50019, Italy.
ChemMedChem
|February 5, 2025
概括
增长差异化因子15 (GDF15) 和它的受体GFRAL是能量平衡和食欲的关键. 针对这种途径为肥胖和与癌症有关的浪费提供了新的治疗方法.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 增长差异化因子15 (GDF15) 是TGF-β超级家族中的一种细胞因子,具有不同的生理和病理作用.
- 循环GDF15水平在各种条件下增加,包括衰老,怀孕,癌症,心血管疾病和感染.
- GDF15主要通过大脑干中的GFRAL受体产生厌食症和缓解症等效应,涉及RET共受体对能量稳定和恶心进行信号传递.
研究的目的:
- 审查了解GDF15-GFRAL信号的最新进展.
- 总结生物活性GDF15衍生分子及其药理应用.
- 探索针对GDF15-GFRAL通路的治疗策略,用于诸如肥胖和癌症缓解症等疾病.
主要方法:
- 对GDF15-GFRAL信号传导研究的文献综述.
- 对GFRAL分布和GDF15更广泛的作用的最新发现的分析.
- 使用GDF15类似物和的治疗方法的总结.
主要成果:
- GDF15-GFRAL信号传递对能量恒温和恶心诱导至关重要.
- 更广泛的GFRAL分布表明不同的GDF15功能.
- 两种治疗策略正在出现:GDF15类似物作为肥胖的GFRAL激动剂和GDF15对的对抗剂.
结论:
- GDF15-GFRAL通路具有显著的治疗潜力.
- 准这种途径可能会导致针对肥胖,癌症缓解症和相关疾病的新型治疗方法.
- 需要进一步研究与GDF15相关的疾病及其治疗.
相关概念视频
Transducer Mechanism: G Protein–Coupled Receptors
1.8K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
1.8K
G Protein-coupled Receptors
11.2K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
11.2K
GPCRs Regulate Adenylyl Cylase Activity
5.2K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.2K
Activation and Inactivation of G Proteins
6.6K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.6K
GPCR Desensitization
5.7K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.7K
G-protein Coupled Receptors
114.9K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
114.9K


