揭示LRP1在阿尔茨海默病中的作用:关注Aβ清除和肝脑轴

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wanyue Yang, Zilin Wei, Tianhui Wang
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引用次数: 0

摘要

阿尔茨海默病(AD)是最普遍的痴呆症形式,对全球健康负担造成重大影响。淀粉样蛋白- β (Aβ)斑块和tau蛋白缠结的逐渐积累会引发神经炎症、氧化应激和神经元损伤,因此迫切需要有效的清除机制。最近的研究发现,低密度脂蛋白受体相关蛋白1 (LRP1)是调节a β清除、神经炎症和血脑屏障完整性的关键因素,特别是与肝脑轴相关的因素。本文综述了LRP1在AD中的作用,重点关注其在大脑和肝脏中的表达,对a β代谢的贡献,以及作为治疗靶点的潜力。通过系统的文献综述,研究人员探索了LRP1在各种生物过程中的多方面作用,包括其参与a β转运、肝脏清除和神经炎症调节。此外,研究了体育锻炼、药物干预和饮食因素对LRP1表达水平的影响,阐明了这些方法如何增强Aβ清除。研究结果表明,随着AD的进展,LRP1的表达会逐渐降低,而增加LRP1的活性——特别是通过运动和药物治疗——可以提高Aβ的清除率,减少神经炎症反应。此外,LRP1参与肝脑轴显示其在AD病理中更广泛的全身性作用。总之,靶向LRP1为AD的预防和治疗提供了一条有希望的途径,为通过肝-脑轴增强a β清除途径的治疗潜力提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the Role of LRP1 in Alzheimer’s Disease: A Focus on Aβ Clearance and the Liver-Brain Axis

Alzheimer’s disease (AD) is the most prevalent form of dementia, significantly contributing to the global health burden. The progressive accumulation of amyloid-beta (Aβ) plaques and tau tangles triggers neuroinflammation, oxidative stress, and neuronal damage, highlighting the critical need for effective clearance mechanisms. Recent research has identified low-density lipoprotein receptor-related protein 1 (LRP1) as a key factor in the regulation of Aβ clearance, neuroinflammation, and blood–brain barrier integrity, particularly in relation to the liver-brain axis. This review provides a comprehensive examination of the role of LRP1 in AD, focusing on its expression in the brain and liver, its contribution to Aβ metabolism, and its potential as a therapeutic target. Using a systematic literature review, LRP1’s multifaceted roles across various biological processes were explored, including its involvement in Aβ transport, clearance via the liver, and modulation of neuroinflammation. Additionally, the impact of physical exercise, pharmacological interventions, and dietary factors on LRP1 expression levels was investigated, elucidating how these approaches may enhance Aβ clearance. The findings demonstrate that LRP1 expression decreases progressively as AD advances, and that augmenting LRP1 activity—particularly through exercise and drug therapies—can improve Aβ clearance and reduce neuroinflammatory responses. Furthermore, LRP1’s involvement in the liver-brain axis reveals its broader systemic role in AD pathology. In conclusion, targeting LRP1 offers a promising avenue for AD prevention and treatment, providing new insights into the therapeutic potential of enhancing Aβ clearance pathways through the liver-brain axis.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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