title: The p38 mitogen-activated protein kinase signaling pathway is involved in regulating low-density lipoprotein receptor-related protein 1-mediated β-amyloid protein internalization in mouse brain.
abstract: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Recently, increasing evidence suggests that intracellular β-amyloid protein (Aβ) alone plays a pivotal role in the progression of AD. Therefore, understanding the signaling pathway and proteins that control Aβ internalization may provide new insight for regulating Aβ levels. In the present study, the regulation of Aβ internalization by p38 mitogen-activated protein kinases (MAPK) through low-density lipoprotein receptor-related protein 1 (LRP1) was analyzed in vivo. The data derived from this investigation revealed that Aβ1-42 were internalized by neurons and astrocytes in mouse brain, and were largely deposited in mitochondria and lysosomes, with some also being found in the endoplasmic reticulum. Aβ1-42-LRP1 complex was formed during Aβ1-42 internalization, and the p38 MAPK signaling pathway was activated by Aβ1-42 via LRP1. Aβ1-42 and LRP1 were co- localized in the cells of parietal cortex and hippocampus. Furthermore, the level of LRP1-mRNA and LRP1 protein involved in Aβ1-42 internalization in mouse brain. The results of this investigation demonstrated that Aβ1-42 induced an LRP1-dependent pathway that related to the activation of p38 MAPK resulting in internalization of Aβ1-42. These results provide evidence supporting a key role for the p38 MAPK signaling pathway which is involved in the regulation of Aβ1-42 internalization in the parietal cortex and hippocampus of mouse through LRP1 in vivo.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Kai-Ge
authors.initials: KG
authors.lastname: Ma
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Hu
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, 1 Xinwang road, Xi'an, 710021, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Chang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an Jiaotong University Health Science Center,76 Yanta West Road, Xi'an, 710061, China.
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an Jiaotong University Health Science Center,76 Yanta West Road, Xi'an, 710061, China. Electronic address: qianyh38@mail.xjtu.edu.cn.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qian
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an Jiaotong University Health Science Center,76 Yanta West Road, Xi'an, 710061, China. Electronic address: wn_yang@mail.xjtu.edu.cn.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Yang
authors.affiliation: Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China. Electronic address: quqiumin@hotmail.com.
authors.forename: Qiu-Min
authors.initials: QM
authors.lastname: Qu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D020935:MAP Kinase Signaling System; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D010446:Peptide Fragments; D012333:RNA, Messenger; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; C075222:amyloid beta-protein (1-42); D048051:p38 Mitogen-Activated Protein Kinases
keywords: Alzheimer’s disease; Beta-amyloid protein; Internalization; Low-density lipoprotein receptor-related protein 1; p38 mitogen-activated protein kinase signaling pathway