在阿尔茨海默病中,UFMylation通路受损
Tingxiang Yan1, Michael G Heckman2, Emily C Craver2
1Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.
Molecular neurodegeneration
|December 19, 2024
概括
阿尔茨海默病的大脑显示UFM1蛋白水平增加,与tau病理有关. 准UFSP2可能会减少超UFMylation,但操纵这种途径的风险需要研究.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 遗传学 是一个遗传学.
背景情况:
- 阿尔茨海默病 (AD) 的特点是团和β-粉样蛋白斑块.
- 在阿尔茨海默病的发病过程中,UFM1 (一种类似于乌比奎丁的蛋白质) 的作用尚未得到充分研究.
- 在实验模型中,UFMylation修改了tau聚合,但其在人类AD大脑中的作用尚不清楚.
研究的目的:
- 研究人类AD大脑中UFM1通路的变化.
- 确定UFMylation和AD神经病理学之间的关联.
- 探索UFMylation,细胞应激和tau病理之间的功能联系.
主要方法:
- 分析了来自AD和对照病例的人类额叶和皮层的UFM1通路蛋白水平.
- 使用多变量回归和邦费罗尼校正来评估与神经病理学和生化标志物的关联.
- 与RNAseq数据相关联的UFMylation和基因编辑神经元 (CRISPR-Cas9) 中的验证结果.
主要成果:
- 人类AD大脑表现出增加的UFM1蛋白水平,主要是结合的UFM1 (超UFMylation).
- 在阿尔茨海默氏症大脑区域,UFMylation与病理性tau有很强的相关性.
- 结合的UFM1水平与UFSP2 (deUFMylation酶) 有负相关性;UFM1/UFSP2的变化扰乱了DNA损伤,并在神经元中展开了蛋白质反应.
结论:
- 在人类AD大脑中,UFM1途径发生显著变化.
- 似乎UFMylation级联修改了AD中的tau病理.
- UFSP2是减少超UFMylation的潜在目标;途径操纵的风险需要进一步调查.
关键词:
阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.脑子 脑子 脑子 脑子塔乌·塔乌 (Tau Tau) 是一个在UFM1中,UFM1是UFM1.在UFMylation中进行化.在UFSP2中,UFSP2是UFSP2.更多相关视频
08:25Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
3.2K
06:44Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)
Published on: January 10, 2025
428
相关概念视频
01:26Alzheimer's Disease: Overview
444
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...
444
01:22Alzheimer's Disease: Treatment
162
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...
162
03:03Amyloid Fibrils
9.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
01:37The Unfolded Protein Response
4.4K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.4K