The Low‐Density Lipoprotein Receptor‐Related Protein, a Multifunctional Apolipoprotein E Receptor, Modulates Hippocampal Neurite Development
: The ε4 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 neu...
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Published in | Journal of neurochemistry Vol. 68; no. 2; pp. 587 - 595 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.02.1997
Blackwell |
Subjects | |
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Abstract | : The ε4 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. |
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AbstractList | 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. The ε4 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. 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 serumcontaining 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. : The ε4 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. |
Author | Holtzman, David M. Bu, Guojun Schwartz, Alan L. Narita, Masaaki |
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Keywords | Neurite Alzheimer disease Rodentia Central nervous system In vitro Lipoprotein LDL Vertebrata Mammalia Neuron Mouse Apolipoprotein E Development Hippocampus Brain (vertebrata) Biological receptor |
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Snippet | : The ε4 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... 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... The ε4 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... |
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SubjectTerms | 39‐kDa protein Alzheimer's disease Animals Antibodies - pharmacology Apolipoprotein E Apolipoprotein E‐deficient mice Apolipoproteins - analysis Apolipoproteins - physiology Astrocytes - chemistry Astrocytes - physiology Biological and medical sciences Blood Proteins - pharmacology Carrier Proteins - analysis Carrier Proteins - pharmacology Cell Division - drug effects Cell Division - physiology Cells, Cultured - chemistry Cells, Cultured - physiology Fetus - cytology Fundamental and applied biological sciences. Psychology Glycoproteins - analysis Glycoproteins - pharmacology Hippocampus - cytology Isolated neuron and nerve. Neuroglia LDL-Receptor Related Protein-Associated Protein Ligands Lipoprotein receptor‐related protein Low Density Lipoprotein Receptor-Related Protein-1 Mice Mice, Inbred C57BL Mice, Mutant Strains Molecular Chaperones - analysis Neurite outgrowth Neurites - chemistry Neurites - physiology Neurons - chemistry Neurons - ultrastructure Rabbits Receptors, Immunologic - analysis Receptors, Immunologic - immunology Receptors, Immunologic - physiology Receptors, LDL - analysis Receptors, LDL - physiology Receptors, Lipoprotein - analysis Receptors, Lipoprotein - physiology Subcellular Fractions - chemistry Vertebrates: nervous system and sense organs |
Title | The Low‐Density Lipoprotein Receptor‐Related Protein, a Multifunctional Apolipoprotein E Receptor, Modulates Hippocampal Neurite Development |
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