关键词: Alzheimer’s disease Alzheimer’s disease animal models Amyloid-β Cognitive function Rotating magnetic field

Mesh : Animals Alzheimer Disease / metabolism therapy Mice Amyloid beta-Peptides / metabolism Cognitive Dysfunction Mice, Transgenic Magnetic Fields Disease Models, Animal Plaque, Amyloid Brain / metabolism

来  源:   DOI:10.24272/j.issn.2095-8137.2024.034   PDF(Pubmed)

Abstract:
Amyloid beta (Aβ) monomers aggregate to form fibrils and amyloid plaques, which are critical mechanisms in the pathogenesis of Alzheimer\'s disease (AD). Given the important role of Aβ1-42 aggregation in plaque formation, leading to brain lesions and cognitive impairment, numerous studies have aimed to reduce Aβ aggregation and slow AD progression. The diphenylalanine (FF) sequence is critical for amyloid aggregation, and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings. In this study, we examined the effects of a moderate-intensity rotating magnetic field (RMF) on Aβ aggregation and AD pathogenesis. Results indicated that the RMF directly inhibited Aβ amyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro. Using the AD mouse model APP/PS1, RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments, including exploration and spatial and non-spatial memory abilities. Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation, attenuated microglial activation, and reduced oxidative stress in the APP/PS1 mouse brain. These findings suggest that RMF holds considerable potential as a non-invasive, high-penetration physical approach for AD treatment.
淀粉样β蛋白(Aβ)单体聚集形成纤维和淀粉样斑块,是阿尔茨海默病(AD)发病的重要机制之一。由于Aβ1-42聚集在斑块形成中起着重要作用,最终导致患者的脑损伤和认知障碍,越来越多的研究致力于减少Aβ聚集过程以减缓AD进展。二苯丙氨酸(FF)序列对淀粉样蛋白聚集至关重要,并且已有研究证明由于芳香环的抗磁性各向异性,导致了磁场可以影响肽的取向。在本研究中,我们使用中等强度的旋转磁场(RMF)来探索其对Aβ的聚集和AD发病过程。我们的数据显示RMF可以直接抑制Aβ淀粉样蛋白纤维的形成并降低Aβ诱导的体外神经细胞毒性。使用AD小鼠模型APP / PS1,我们发现RMF可以将其运动能力恢复到健康对照小鼠的水平。AD小鼠的认知障碍,包括探索能力、空间和非空间记忆能力也得到了显著缓解。组织切片实验结果显示,RMF 减少了APP/PS1小鼠大脑内淀粉样斑块的积聚,减弱了小胶质细胞的活化,并降低了其海马组织内氧化应激水平。因此,我们的数据表明 RMF 具有巨大的潜力,可以开发为一种用于治疗AD的非侵入性、高渗透性的物理方法。.
摘要:
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