Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein
| Autor: | Fei Shen, Gene K. Wong, Gregory J. Brewer, Yanwen Jiang, Britto P. Nathan, Robert G. Struble |
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| Rok vydání: | 2002 |
| Předmět: |
Gene isoform
Apolipoprotein E Male medicine.medical_specialty Neurite Apolipoprotein B Apolipoprotein E4 Apolipoprotein E3 Cell Culture Techniques Biology Mice Apolipoproteins E Alzheimer Disease Internal medicine medicine Neurites Animals LDL-Receptor Related Protein-Associated Protein Molecular Biology Cells Cultured Cerebral Cortex Mice Knockout Neuronal Plasticity Dose-Response Relationship Drug General Neuroscience Cell Differentiation Embryonic stem cell Immunohistochemistry Nerve Regeneration Lactoferrin Endocrinology medicine.anatomical_structure Cerebral cortex Culture Media Conditioned LDL receptor biology.protein lipids (amino acids peptides and proteins) Female Neurology (clinical) Low Density Lipoprotein Receptor-Related Protein-1 Developmental Biology Lipoprotein |
| Zdroj: | Brain research. 928(1-2) |
| ISSN: | 0006-8993 |
| Popis: | The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer’s disease (AD); however, the mechanism is unknown. We previously demonstrated that apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the present study we examined the effects of apoE on neurite outgrowth from cultured adult mouse cortical neurons to examine if adult neurons respond the same way that embryonic cells do. The results from this study demonstrated that (1) cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have significantly shorter neurites than neurons from adult wild-type (WT) mice; (2) incubation of cortical neurons from adult apoE KO mice with human apoE3 increased neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent fashion; (3) the isoform specific effects were abolished by incubation of the neurons with either receptor associated protein (RAP) or lactoferrin, both of which block the interaction of apoE-containing lipoproteins with the low-density lipoprotein receptor-related protein (LRP). These data suggest a potential mechanism whereby apoE4 may play a role in regenerative failure and accelerate the development of AD. |
| Databáze: | OpenAIRE |
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