Abstract
The epsilon 4 allele of apolipoprotein E (apoE) is an important risk factor for Alzheimer's disease. A major neuronal receptor for apoE within the brain is the low-density lipoprotein receptor-related protein (LRP). Using primary cultured hippocampal neurons, we examined the role of LRP in early neuronal development. LRP, as well as a 39-kDa protein that regulates its activity, is localized abundantly in developing neurons. Both the 39-kDa protein and an anti-LRP antibody inhibited neurite outgrowth of primary hippocampal neurons cultured in either serum-containing medium or on cortical astrocyte monolayers in serum-free medium. It is noteworthy that microtubule-associated protein-2 immunoreactive process outgrowth was decreased significantly in hippocampal neurons cultured on cortical astrocytes derived from apoE-deficient mice and was not diminished further following incubation with LRP inhibitors. Thus, these results suggest that LRP can influence aspects of neuronal process development and that apoE-containing lipoproteins may be one of the major LRP ligands that can contribute to this process.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies / pharmacology
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Apolipoproteins / analysis
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Apolipoproteins / physiology
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Astrocytes / chemistry
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Astrocytes / physiology
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Blood Proteins / pharmacology
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Carrier Proteins / analysis
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Carrier Proteins / pharmacology
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Cell Division / drug effects
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Cell Division / physiology
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Cells, Cultured / chemistry
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Cells, Cultured / physiology
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Fetus / cytology
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Glycoproteins / analysis
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Glycoproteins / pharmacology
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Hippocampus / cytology*
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LDL-Receptor Related Protein-Associated Protein
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Ligands
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Low Density Lipoprotein Receptor-Related Protein-1
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Molecular Chaperones / analysis
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Neurites / chemistry*
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Neurites / physiology
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Neurons / chemistry
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Neurons / ultrastructure
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Rabbits
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Receptors, Immunologic / analysis
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Receptors, Immunologic / immunology
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Receptors, Immunologic / physiology*
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Receptors, LDL / analysis
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Receptors, LDL / physiology
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Receptors, Lipoprotein / analysis
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Receptors, Lipoprotein / physiology*
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Subcellular Fractions / chemistry
Substances
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Antibodies
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Apolipoproteins
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Blood Proteins
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Carrier Proteins
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Glycoproteins
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LDL-Receptor Related Protein-Associated Protein
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Ligands
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Low Density Lipoprotein Receptor-Related Protein-1
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Molecular Chaperones
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Receptors, Immunologic
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Receptors, LDL
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Receptors, Lipoprotein