N5-((perfluorophenyl)amino)glutamine regulates BACE1, tau phosphorylation, synaptic function, and neuroinflammation in Alzheimer's disease models.

IF 5.7 4区 生物学 Q1 BIOLOGY
Bioscience trends Pub Date : 2025-03-06 Epub Date: 2025-01-25 DOI:10.5582/bst.2024.01360
Jun-Sik Kim, Yongeun Cho, Jeongmi Lee, Heewon Cho, Sukmin Han, Yeongyeong Lee, Yeji Jeon, Tai Kyoung Kim, Ju-Mi Hong, Jeonghyeong Im, Minshik Chae, Yujeong Lee, Hyunwook Kim, Sang Yoon Park, Sung Hyun Kim, Joung Han Yim, Dong-Gyu Jo
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引用次数: 0

Abstract

Alzheimer's disease (AD) is the most common type of dementia. Its incidence is rising rapidly as the global population ages, leading to a significant social and economic burden. AD involves complex pathologies, including amyloid plaque accumulation, synaptic dysfunction, and neuroinflammation. This study explores the therapeutic potential of N 5 -((perfluorophenyl)amino)glutamine (RA-PF), a derivative of γ-glutamyl-N'-(2-hydroxyphenyl)hydrazide (Ramalin), a compound with antioxidant and anti-inflammatory properties. Administration of RA-PF to 5xFAD mice decreases BACE1, reduces Aβ plaque deposition, inhibits microglial activation, restores synaptic transmission, and improves mitochondrial motility, leading to the recovery of cognitive function. Additionally, RA-PF treatment in 3xTg-AD mice alleviates anxiety-like behaviors, tau phosphorylation via inactivating GSK-3β, and BACE1 expression. Further transcriptomic analysis reveals RA-PF treatment in AD mice models recovers phagosome, inflammation, NOD-like receptor, presynaptic membrane, and postsynaptic membrane related signaling pathways. These findings suggest that RA-PF effectively targets multiple aspects of AD pathology, offering a novel multi-target approach for AD treatment.

阿尔茨海默病(AD)是最常见的痴呆症类型。随着全球人口老龄化,其发病率正在迅速上升,造成了重大的社会和经济负担。AD涉及复杂的病理,包括淀粉样斑块积聚、突触功能障碍和神经炎症。本研究探讨了n5 -(全氟苯基)氨基)谷氨酰胺(RA-PF)的治疗潜力,它是γ-谷氨酰胺-N'-(2-羟基苯基)肼(Ramalin)的衍生物,具有抗氧化和抗炎特性。给5xFAD小鼠给予RA-PF可降低BACE1,减少Aβ斑块沉积,抑制小胶质细胞活化,恢复突触传递,改善线粒体运动,从而恢复认知功能。此外,在3xTg-AD小鼠中,RA-PF治疗通过灭活GSK-3β和BACE1表达来减轻焦虑样行为、tau磷酸化。进一步的转录组学分析显示,RA-PF治疗在AD小鼠模型中恢复了吞噬体、炎症、nod样受体、突触前膜和突触后膜相关的信号通路。这些发现表明,RA-PF有效靶向AD病理的多个方面,为AD治疗提供了一种新的多靶点方法。
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来源期刊
CiteScore
13.60
自引率
1.80%
发文量
47
审稿时长
>12 weeks
期刊介绍: BioScience Trends (Print ISSN 1881-7815, Online ISSN 1881-7823) is an international peer-reviewed journal. BioScience Trends devotes to publishing the latest and most exciting advances in scientific research. Articles cover fields of life science such as biochemistry, molecular biology, clinical research, public health, medical care system, and social science in order to encourage cooperation and exchange among scientists and clinical researchers.
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