低密度脂蛋白受体相关蛋白1：在阿尔茨海默病中促进β淀粉样蛋白流出转运体的机制及作用
The LDL Receptor-Related Protein 1: Mechanisms and roles in promoting Aβ efflux transporter in Alzheimer's disease.
作者信息
Li Weiyi, Chen Canyu, Xu Bo, Chen Jixiang, Yang Mingxia, Gao Lili, Zhou Jiecan
机构信息
The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, China.
The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
出版信息
Biochem Pharmacol. 2025 Jan;231:116643. doi: 10.1016/j.bcp.2024.116643. Epub 2024 Nov 20.
The LDL Receptor-Related Protein 1(LRP1), a member of the Low-density Lipoprotein (LDL) receptor family, is a multifunctional cellular transporter and signaling receptor, this includes regulation of lipid metabolism, cell migration and signaling. Abnormal accumulation of amyloid beta (Aβ) in the brain is thought to be the main pathological change in Alzheimer's disease. By binding to a variety of ligands, LRP1 is involved in the internalization and degradation of Aβ, thereby affecting the course of Alzheimer's disease (AD). Here, we discuss the main mechanisms by which LRP1 mediates Aβ degradation and clearance and several current therapeutic approaches targeting LRP1. Finally, we concluded that modulating the expression level of LRP1 is an effective way to attenuate Aβ deposition and ameliorate AD. Abbreviations: LRP1, LDL Receptor-Related Protein 1;LDL, Low Density Lipoprotein; Aβ, amyloid beta; AD, Alzheimer's disease; APP, amyloid precursor protein; ApoE, apolipoprotein E; TGF, growth factor; MMP, matrix metalloproteinase;TAT, thrombin-antithrombin complex; BBB, blood-brain barrier; MMP-9,cyclophilin A (CypA)-matrix metalloproteinase-9; VMC, Vascular Mural Cell; IDE,insulin degrading enzyme; EVs, extracellular vesicles; sLRP1,shed LRP1; BDNF, brain-derived neurotrophin; IGF-1,insulin-like growth factor 1; NGF, nerve growth factor; MAPK,mitogen-activated protein kinase; ERK1/2,exogenous signal-regulated kinase1/2;JNK, c-Jun amino-terminal kinase; TLR4, toll-like receptor 4; NF-κB,nuclear factor-κB; GCAP,guanylate cyclase-activating protein; KD, ketogenic diet;KB, ketone body; BLECs,Brain-like endothelial cell; BYHWD, Buyang Huanwu decoction; LGZG, Linguizhugan decoction;P- gp, P-glycoprotein;PPARγ, Peroxisome proliferator-activated receptor γ;SP16,SERPIN peptide 16; Asx, Astaxanthin; Bex, Bexarotene.
低密度脂蛋白受体相关蛋白1（LRP1）是低密度脂蛋白（LDL）受体家族的成员之一，是一种多功能细胞转运体和信号受体，包括调节脂质代谢、细胞迁移和信号传导。大脑中β淀粉样蛋白（Aβ）的异常积累被认为是阿尔茨海默病的主要病理变化。通过与多种配体结合，LRP1参与Aβ的内化和降解，从而影响阿尔茨海默病（AD）的病程。在此，我们讨论LRP1介导Aβ降解和清除的主要机制以及几种目前针对LRP1的治疗方法。最后，我们得出结论，调节LRP1的表达水平是减轻Aβ沉积和改善AD的有效方法。缩写：LRP1，低密度脂蛋白受体相关蛋白1；LDL，低密度脂蛋白；Aβ，β淀粉样蛋白；AD，阿尔茨海默病；APP，淀粉样前体蛋白；ApoE，载脂蛋白E；TGF，生长因子；MMP，基质金属蛋白酶；TAT，凝血酶 - 抗凝血酶复合物；BBB，血脑屏障；MMP - 9，亲环素A（CypA） - 基质金属蛋白酶 - 9；VMC，血管壁细胞；IDE，胰岛素降解酶；EVs，细胞外囊泡；sLRP1，可溶性LRP1；BDNF，脑源性神经营养因子；IGF - 1，胰岛素样生长因子1；NGF，神经生长因子；MAPK，丝裂原活化蛋白激酶；ERK1/2，细胞外信号调节激酶1/2；JNK，c - Jun氨基末端激酶；TLR4，Toll样受体4；NF - κB，核因子κB；GCAP，鸟苷酸环化酶激活蛋白；KD，生酮饮食；KB，酮体；BLECs，脑样内皮细胞；补阳还五汤；苓桂术甘汤；P - gp，P - 糖蛋白；PPARγ，过氧化物酶体增殖物激活受体γ；SP16，丝氨酸蛋白酶抑制剂肽16；虾青素；贝沙罗汀。
Zotero 插件