微质可以促进或抑制由Aβ1-42寡合体引起的Trail介导的兴奋毒性
Jian Zou1, Elizabeth McNair1, Sagan DeCastro1,2
1Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA.
Journal of neuroinflammation
|September 1, 2024
概括
微质在阿尔茨海默氏症 (AD) 病理学中起着双重作用,既介导神经保护,又介导神经退行. 准微质细胞以促进保护性状态可能为AD预防提供一种新的策略.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 阿尔茨海默病 (AD) 涉及渐进的神经退行和微质激活,导致认知能力下降.
- 可溶性粉样β (Aβ) 寡合体是早期的病理特征,可以诱导兴奋毒性和微质激活.
- 了解微质在Aβ诱导的神经毒性中的作用对于确定治疗点至关重要.
研究的目的:
- 调查海马体中Aβ寡合体诱导的神经毒性的机制.
- 阐明微质和免疫媒介在这个过程中的特定作用.
- 确定潜在的分子点,以促进AD的保护性微质状态.
主要方法:
- 利用海马体内内脑切片培养 (HEBSC) 来建模Aβ寡头毒性.
- 评估了谷氨基基过度兴奋和TNF相关的亡诱导配体 (TRAIL) 信号传导的作用.
- 使用DREADDs操纵的微质激活状态,消耗的CSF1R对抗性,以及重新定居.
主要成果:
- 甲寡合体的神经毒性是由谷氨酸激素过激和 TRAIL 介导的.
- 微质可以加剧和保护Aβ诱导的毒性.
- 重新填充的微质细胞对Aβ神经毒性表现出耐药性,表现出抗炎和营养丰富的表型.
结论:
- 微质是Aβ诱导的神经保护和神经退行症的关键调解者.
- 向保护性表型调节微质,为阿尔茨海默病提供了潜在的预防策略.
- mTORC2和IRF7被确定为潜在的治疗点.
相关概念视频
Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...
Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
Drugs Affecting Neurotransmitter Release or Uptake
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...
Drugs Affecting Neurotransmitter Synthesis
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, which converts...
Alzheimer's Disease: Treatment
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...


