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Mitogen-activated protein kinase signaling pathways promote low-density lipoprotein receptor-related protein 1-mediated internalization of beta-amyloid protein in primary cortical neurons.
Yang, Wei-Na; Ma, Kai-Ge; Qian, Yi-Hua; Zhang, Jian-Shui; Feng, Gai-Feng; Shi, Li-Li; Zhang, Zhi-Chao; Liu, Zhao-Hui.
Afiliação
  • Yang WN; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
  • Ma KG; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
  • Qian YH; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China. Electronic address: qianyh38@mail.xjtu.edu.cn
  • Zhang JS; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
  • Feng GF; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
  • Shi LL; Department of Human Anatomy, Xi'an Medical University, 1 Xinwang Road, Xi'an 710021, China.
  • Zhang ZC; Department of Human Anatomy, Histology and Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
  • Liu ZH; Department of Anatomy and Cytoneurobiology Unit, Medical College of Soochow University, Suzhou 215123, China.
Int J Biochem Cell Biol ; 64: 252-64, 2015 Jul.
Article em En | MEDLINE | ID: mdl-25936756
Mounting evidence suggests that the pathological hallmarks of Alzheimer's disease (AD) are caused by the intraneuronal accumulation of beta-amyloid protein (Aß). Reuptake of extracellular Aß is believed to contribute significantly to the intraneuronal Aß pool in the early stages of AD. Published reports have claimed that the low-density lipoprotein receptor-related protein 1 (LRP1) mediates Aß1-42 uptake and lysosomal trafficking in GT1-7 neuronal cells and mouse embryonic fibroblast non-neuronal cells. However, there is no direct evidence supporting the role of LRP1 in Aß internalization in primary neurons. Our recent study indicated that p38 MAPK and ERK1/2 signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor (α7nAChR)-mediated Aß1-42 uptake in SH-SY5Y cells. This study was designed to explore the regulation of MAPK signaling pathways on LRP1-mediated Aß internalization in neurons. We found that extracellular Aß1-42 oligomers could be internalized into endosomes/lysosomes and mitochondria in cortical neurons. Aß1-42 and LRP1 were also found co-localized in neurons during Aß1-42 internalization, and they could form Aß1-42-LRP1 complex. Knockdown of LRP1 expression significantly decreased neuronal Aß1-42 internalization. Finally, we identified that p38 MAPK and ERK1/2 signaling pathways regulated the internalization of Aß1-42 via LRP1. Therefore, these results demonstrated that LRP1, p38 MAPK and ERK1/2 mediated the internalization of Aß1-42 in neurons and provided evidence that blockade of LRP1 or inhibitions of MAPK signaling pathways might be a potential approach to lowering brain Aß levels and served a potential therapeutic target for AD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Receptores de LDL / Peptídeos beta-Amiloides / Sistema de Sinalização das MAP Quinases / Proteínas Supressoras de Tumor Limite: Animals / Humans Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Receptores de LDL / Peptídeos beta-Amiloides / Sistema de Sinalização das MAP Quinases / Proteínas Supressoras de Tumor Limite: Animals / Humans Idioma: En Revista: Int J Biochem Cell Biol Assunto da revista: BIOQUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China País de publicação: Holanda