title: Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth.
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.
authors.affiliation: Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Keping
authors.initials: K
authors.lastname: Chen
authors.affiliation: Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
authors.affiliation: Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Tianli
authors.initials: T
authors.lastname: Gao
authors.affiliation: Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Xiulei
authors.initials: X
authors.lastname: Xue
authors.affiliation: Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing 210009, China.
authors.forename: Fengqin
authors.initials: F
authors.lastname: Miao
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000502:physiology*; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D019006:Neural Cell Adhesion Molecules
keywords: Alzheimer's disease (AD); amyloid precursor protein (APP); neural cell adhesion molecule (NCAM); neurite outgrowth