摘要
背景:对阿尔茨海默病(AD)和相关疾病缺乏诊断工具和疾病修正治疗方法,统称为同步性疾病,导致流行病比例的社会经济负担。蛋白质组学方法可以用来识别新的蛋白质,帮助我们理解τ相关的病理特征和/或与重言症相关的细胞应激反应的发病机制。然而,这些研究需要考虑到脑区域的特异性和神经变性的分期,以便对已鉴定的蛋白质的病理作用有更深入的了解。方法:采用JNPL 3模型(JNPL 3),表达人τ携带P301L突变,并发生运动损伤,其严重程度与病理τ蓄积增加有关。对JNPL 3小鼠和非转基因小白鼠的组织进行二维凝胶电泳分析。用串联质谱法鉴定了不同含量的蛋白质斑点。采用死后轻度认知障碍(MCI)、AD和正常衰老对照,验证所鉴定蛋白的病理意义。结果:Ezrin是一种蛋白,在τ介导的神经退行性变中被上调。结果表明,JNPL 3小鼠Ezrin蛋白丰度在运动损伤前增加,在严重运动障碍小鼠中维持。MCI和AD患者颞叶皮质Ezrin表达也增加。结论:Ezrin蛋白丰度的增加与神经退行性变的早期和人类疾病的发生有关。了解Ezrin在AD等重言症中的作用,为靶向τ介导的神经变性提供了新的见解。
关键词: 阿尔茨海默病,埃兹林,ERM,τ,神经变性,生物标志物,紧张病。
Current Alzheimer Research
Title:Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse Model and Alzheimer’s Disease
Volume: 15 Issue: 12
关键词: 阿尔茨海默病,埃兹林,ERM,τ,神经变性,生物标志物,紧张病。
摘要: Background: The lack of diagnostic tools and disease-modifying treatments against Alzheimer’s disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular stress responses associated with tauopathy. These studies, however, need to be conducted taking into consideration brain region specificity and stage of neurodegeneration in order to provide insights about the pathological role of the identified proteins.
Methods: We used a tauopathy mouse model (JNPL3) that expresses human tau bearing a P301L mutation and develops motor impairment, the severity of which correlates with the increased accumulation of pathological tau. Tissue was dissected from asymptomatic and severely motor impaired JNPL3 mice as well as non-transgenic littermate controls and subjected to two-dimensional gel electrophoresis. Differentially abundant protein spots were identified by tandem mass spectrometry. Postmortem mild cognitive impairment (MCI), AD and normal aging controls were used to validate the pathological significance of the identified protein.
Results: Ezrin was identified as a protein that is upregulated in tau-mediated neurodegeneration. We demonstrate that Ezrin protein abundance increased in JNPL3 mice preceded motor impairment and was sustained in severely motor impaired mice. Ezrin expression was also increased in the temporal cortex of MCI and AD patients.
Conclusion: The results demonstrate that increased Ezrin protein abundance changes are associated with the early stages of neurodegeneration in tauopathy models and human disease. Understanding the role of Ezrin in tauopathies such as AD may provide new insights for targeting tau-mediated neurodegeneration.
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Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse Model and Alzheimer’s Disease, Current Alzheimer Research 2018; 15 (12) . https://dx.doi.org/10.2174/1567205015666180813152043
DOI https://dx.doi.org/10.2174/1567205015666180813152043 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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