阻断STING激活可以缓解微质功能障碍和广泛的阿尔茨海默氏病病理
Sunwoo Chung1,2, June-Hyun Jeong1,2, Jong-Chan Park3
1Convergence Dementia Research Center, College of Medicine, Seoul National University, 03080, Seoul, Korea.
Experimental & molecular medicine
|September 1, 2024
概括
抑制STING激活可以控制微质细胞,并减少阿尔茨海默病 (AD) 的症状. 这一途径通过促进炎症和DNA检测而加剧神经退行,为AD提供了一个新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 质细胞激活驱动阿尔茨海默病 (AD) 中的神经退行.
- 参与检测外来DNA的cGAS-STING通路,通过引起微质功能障碍和无菌炎症来加剧AD.
- 粉样β和病理导致微质中的DNA释放,激活这种途径.
研究的目的:
- 为了研究cGAS-STING通路在阿尔茨海默氏病的发病过程中的作用.
- 评估抑制AD中的STING激活的治疗潜力.
主要方法:
- 在阿尔茨海默病模型和人类样本中分析cGAS和STING表达.
- 在AppNL-G-F/hTau双敲入小鼠中的STING的药理抑制.
- 在STING抑制后微质细胞的转录组分析.
主要成果:
- 在AD中,STING激活是上调调的,特别是在APOE ε4等位基存在的情况下,并且对于微质炎症反应是必要的.
- 药理性STING抑制改善了AD症状,降低了Aβ负载,陶酸化和微质突触吞.
- STING抑制诱导了微质基因表达的转变,减少了质分裂和神经炎症.
结论:
- cGAS-STING通路是阿尔茨海默病中神经炎症和神经退行症的关键驱动因素.
- 抑制STING为改善AD病理和预防记忆丧失提供了一个有希望的治疗策略.
更多相关视频
09:33Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
7.9K
09:12Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
15.8K
相关概念视频
Alzheimer's Disease: Treatment
170
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...
170
Alzheimer's Disease: Overview
454
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
454
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
110
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.
110
