摘要
神经细胞内淀粉样β-肽(Aβ)的累积是阿尔茨海默病的早期症状,证明了它在AD神经退化的重要作用。这说明了细胞内的Aβ来源于一部分Aβ(那些不分泌的,始终滞留在细胞内的,或者是分泌的Aβ)形成了细胞内Aβ池。大量的细胞和转基因动物模型被建立以研究细胞内Aβ的致病作用和筛选抗Aβ聚集和相关毒性的药物。Aβ聚合物,特别是低聚物,可能会导致突触功能障碍和神经元丢失。从高速方法中筛选,大量的细胞渗透剂减少了细胞内Aβ低聚物,通过阻止Aβ低聚物在体内的形成而对抗其细胞毒性。本文也讨论了Aβ在代替途径的多功能作用和AD治疗的有关临床意义。
关键词: 阿尔茨海默病,聚合物,动物模型,细胞模型,细胞内Aβ,低聚物,神经毒性,突触功能障碍
Current Alzheimer Research
Title:Intracellular Aβ and its Pathological Role in Alzheimer’s Disease: Lessons from Cellular to Animal Models
Volume: 13 Issue: 6
Author(s): Lina Ji, Xi Zhao, Weijie Lu, Qing Zhang, Zichun Hua
Affiliation:
关键词: 阿尔茨海默病,聚合物,动物模型,细胞模型,细胞内Aβ,低聚物,神经毒性,突触功能障碍
摘要: Accumulation of intraneuronal amyloid-β peptide (Aβ) appears to be an early event in Alzheimer's disease (AD), suggesting its important role in the neurodegenerative process of AD. It is indicated that intracellular Aβ originates from a portion of Aβ, which is not secreted and consequently remains intracellular, or alternatively from the secreted Aβ, which is internalized into intracellular Aβ pool. A number of cell and transgenic animal models are established to study the pathological role of intracellular Aβ, and to screen for drugs against Aβ aggregation and associated toxicity. Aβ aggregates, particularly oligomers, may lead to synaptic dysfunction and neuronal loss. Screened from high-throughput methods, a number of cellpermeable agents reduce the aggregation of intracellular Aβ and antagonize its cytotoxicity by inhibiting the formation of Aβ oligomers in vivo. The multi-functional roles of Aβ in alternate pathways and associated clinical implications for AD treatment are also discussed.
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Cite this article as:
Lina Ji, Xi Zhao, Weijie Lu, Qing Zhang, Zichun Hua , Intracellular Aβ and its Pathological Role in Alzheimer’s Disease: Lessons from Cellular to Animal Models, Current Alzheimer Research 2016; 13 (6) . https://dx.doi.org/10.2174/1567205013666160322142226
DOI https://dx.doi.org/10.2174/1567205013666160322142226 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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