Oncotarget

Research Papers:

Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth

Keping Chen _, Huixia Lu, Tianli Gao, Xiulei Xue, Chunling Wang and Fengqin Miao

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Oncotarget. 2016; 7:14199-14206. https://doi.org/10.18632/oncotarget.7348

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Abstract

Keping Chen1, Huixia Lu1, Tianli Gao1, Xiulei Xue1, Chunling Wang1, Fengqin Miao2

1Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China

2Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing 210009, China

Correspondence to:

Keping Chen, e-mail: [email protected]

Keywords: amyloid precursor protein (APP), neural cell adhesion molecule (NCAM), neurite outgrowth, Alzheimer's disease (AD)

Received: December 24, 2015     Accepted: January 29, 2016     Published: February 12, 2016

ABSTRACT

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. The main features of AD are the pathological changes of density and distribution of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. The processing of amyloid beta precursor protein (APP) to β-amyloid peptide (Aβ) is one of the critical events in the pathogenesis of AD. In this study, we evaluated the role of the interaction of neural cell adhesion molecule (NCAM) and APP in neurite outgrowth using two different experimental systems: PC12E2 cells and hippocampal neurons that were isolated from wild type, APP knock-in and APP knock-out mice. PC12E2 cells or hippocampal neurons were co-cultured with NCAM-negative or NCAM-positive fibroblasts L929 cells. We found that APP promoted neurite outgrowth of PC12E2 cells and hippocampal neurons in either the presence or absence of NCAM. Secreted APP can rescue the neurite outgrowth in hippocampal neurons from APP knock-out mice. The interaction of APP and NCAM had synergic effect in promoting neurite outgrowth in both PC12E2 cells and hippocampal neurons. Our results suggested that the interaction of APP with NCAM played an important role in AD development and therefore could be a potential therapeutic target for AD treatment.


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