突触囊泡糖蛋白2C增强了多巴胺的囊泡储存,并抵消了多巴胺毒性的毒性
Meghan L Bucher1, Amy R Dunn2,3, Joshua M Bradner1,2,4
1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.
The European journal of neuroscience
|March 27, 2024
概括
突触囊泡糖蛋白2C (SV2C) 增强了囊泡中的多巴胺储存,保护了脆弱的多巴胺神经元. 删除SV2C增加了对神经毒素的敏感性,这表明SV2C增加了神经毒素的敏感性.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 神经药理学神经药理学
背景情况:
- 多巴氨基神经元面临高氧化压力,使它们变得脆弱.
- 损害多巴胺储存增加神经毒性,导致帕金森病.
- 突触囊泡糖蛋白2C (SV2C) 之前被确定为囊泡多巴胺功能的修饰剂.
研究的目的:
- 调查SV2C在调节膀性多巴胺动态中的作用.
- 为了确定SV2C是否会影响囊泡中多巴胺和神经毒素的储存.
- 评估SV2C遗传除对小鼠MPTP诱导的神经毒性的影响.
主要方法:
- 在体外测试中使用假光神经递质206 (FFN206) 来可视化SV2C对膀性多巴胺动态的影响.
- 使用放射性标记多巴胺来评估SV2C对孤立囊泡中多巴胺保留的影响.
- 研究了SV2C在囊泡中储存神经毒剂MPP+中的作用.
- 研究了SV2C遗传除对小鼠MPTP诱导的神经退行症的影响.
主要成果:
- 发现SV2C可以促进FFN206在囊泡中的吸收和保留.
- SV2C增强了多巴胺在囊泡区内的保留.
- SV2C增加了囊泡储存神经毒剂MPP+的能力.
- 对SV2C的遗传切除导致小鼠对MPTP诱导的神经毒性的脆弱性增加.
结论:
- 在增强多巴胺的囊泡储存方面,SV2C起着至关重要的作用.
- 此外,SV2C还促进了神经毒素在囊泡中的储存.
- 这些SV2C的功能有助于维护多巴胺基神经元的完整性.
- 准SV2C可能为帕金森病提供治疗策略.
相关概念视频
Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K
Drugs Affecting Neurotransmitter Release or Uptake
1.0K
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.0K
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
288
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...
288
Fusion of Secretory Vesicles with the Plasma Membrane
11.1K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.1K
Overview of Secretory Vesicles
8.5K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.5K
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K


