G蛋白结合受体146:从遗传学和模型系统的新见解
Umesh Tharehalli1, Antoine Rimbert2
1Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Current opinion in lipidology
|March 11, 2024
概括
G蛋白结合受体146 (GPR146) 显示出治疗高胆固醇和动脉样硬化的前景. 研究正在探索其遗传联系,功能和作为心血管疾病新型治疗点的潜力.
科学领域:
- 心血管科学 心血管科学
- 代谢研究研究 代谢研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 动脉样硬化心血管疾病仍然是全球主要的死亡原因.
- 需要新的策略来管理失脂症,特别是耐火性病例或具有不良影响的病例.
- G蛋白结合受体146 (GPR146) 被确定为高胆固醇和动脉样硬化的潜在治疗标.
研究的目的:
- 审查目前关于GPR146的知识,包括遗传证据和功能见解.
- 总结一下GPR146对心脏代谢健康的影响.
- 突出了解GPR146在脂质调节中的作用以及其他方面的最新进展.
主要方法:
- 对将GPR146变异与脂质水平和代谢参数联系起来的人类遗传研究的分析.
- 研究GPR146在脂肪细胞分化,脂解和炎症中的作用.
- 审查正在进行的GPR146脱的努力,并确定其天然配体.
主要成果:
- 人类遗传数据表明,GPR146变体与改变的血脂质谱之间存在相关性.
- GPR146影响了超出脂质调节的代谢过程,包括脂肪生成和炎症途径.
- 正在调查潜在的配体和下游Gαi合途径的识别.
结论:
- 了解GPR146的遗传基础和肝外功能对于治疗开发至关重要.
- 进一步研究GPR146的天然配体和抑制作用至关重要.
- 对于高胆固醇血症和动脉样硬化的创新治疗,GPR146是一个有前途的目标.
相关概念视频
G Protein-coupled Receptors
12.0K
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...
12.0K
Transducer Mechanism: G Protein–Coupled Receptors
2.0K
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,...
2.0K
GPCR Desensitization
6.0K
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...
6.0K
G-protein Coupled Receptors
118.8K
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.
118.8K
Activation and Inactivation of G Proteins
7.1K
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...
7.1K


