二酶2及其同型A作为中枢神经系统疾病中的治疗点
Sanjay K Metkar1, Yuqing Yan1, Yue Lu1
1Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
CNS & neurological disorders drug targets
|October 19, 2023
概括
二酶-2 (PDE2) 抑制剂通过调节循环腺单酸盐 (cAMP) 和循环单酸盐 (cGMP) 信号通路,为中枢神经系统疾病提供了一个有前途的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 循环腺单酸盐 (cAMP) 和循环单酸盐 (cGMP) 是细胞信号传输中的关键的第二信使.
- 固酶 (PDEs),特别是PDE-2 (PDE2A),调节细胞内cAMP和cGMP的水平.
- 失调的cAMP和cGMP信号与各种神经和精神疾病有关.
研究的目的:
- 审查PDE-2在神经精神病,神经退行性和神经发育障碍中的作用.
- 探索PDE-2抑制剂治疗中枢和外周神经系统疾病的治疗潜力.
- 突出需要开发新的PDE2向药物.
主要方法:
- 对研究PDE-2功能和抑制的文献综述.
- 分析PDE-2活性与神经系统疾病病理之间的关系.
- 关于PDE-2抑制剂作为治疗剂的当前研究的摘要.
主要成果:
- 药理上抑制PDE2A可增强中枢神经系统中cAMP和cGMP的信号传递.
- 通过PDE-2抑制剂对这些途径的调节显示出治疗阿尔茨海默氏症,帕金森症和发育障碍等疾病的潜力.
- 对这些疾病的现有治疗方法有限,这增加了对创新的治疗方法的需求.
结论:
- PDE-2 抑制剂代表了一系列神经和精神疾病的有希望的治疗途径.
- 准PDE2A提供了一种恢复正常cAMP和cGMP信号传输的策略,解决未满足的医疗需求.
- 为了有效治疗疾病,需要进一步开发下一代PDE2抑制剂.
相关概念视频
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
02:54Protein Kinases and Phosphatases
13.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.2K
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
318
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
318
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
698
Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
698
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
131
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
131
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K