Petralla Sabrina, Panayotova Maria, Franchina Elisa, Fricker Gert, Puris Elena
Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany.
Pharmaceutics. 2024 Jul 17;16(7):948. doi: 10.3390/pharmaceutics16070948.
Alzheimer's disease (AD) is a progressive neurodegenerative disease impacting the lives of millions of people worldwide. The formation of amyloid β (Aβ) plagues in the brain is the main pathological hallmark of AD. The Aβ deposits are formed due to the imbalance between the production and Aβ clearance in the brain and across the blood-brain barrier (BBB). In this respect, low-density lipoprotein receptor-related protein 1 (LRP1) plays a significant role by mediating both brain Aβ production and clearance. Due to its important role in AD pathogenesis, LRP1 is considered an attractive drug target for AD therapies. In the present review, we summarize the current knowledge about the role of LRP1 in AD pathogenesis as well as recent findings on changes in LRP1 expression and function in AD. Finally, we discuss the advances in utilizing LRP1 as a drug target for AD treatments as well as future perspectives on LRP1 research.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,影响着全球数百万人的生活。大脑中β淀粉样蛋白(Aβ)斑块的形成是AD的主要病理标志。Aβ沉积物的形成是由于大脑中以及血脑屏障(BBB)处Aβ产生与清除之间的失衡所致。在这方面,低密度脂蛋白受体相关蛋白1(LRP1)通过介导大脑Aβ的产生和清除发挥重要作用。由于其在AD发病机制中的重要作用,LRP1被认为是AD治疗的一个有吸引力的药物靶点。在本综述中,我们总结了目前关于LRP1在AD发病机制中的作用的知识,以及AD中LRP1表达和功能变化的最新发现。最后,我们讨论了将LRP1用作AD治疗药物靶点的进展以及LRP1研究的未来前景。