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Thematic Review |
* Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115
1 To whom correspondence should be addressed. e-mail: Uwe.Beffert{at}UTSouthwestern.edu (U.B.); Joachim.Herz{at}UTSouthwestern.edu (J.H.)
The LDL receptor (LDLR) family is comprised of several multifunctional cell surface proteins that bind and endocytose ligands with diverse biological functions. One ligand common to all LDLR family members is apolipoprotein E (apoE), a lipid transport protein that also plays a central role in the pathogenesis of neurodegeneration in Alzheimer's disease.
This review discusses the role of apoE and its receptors in the central nervous system and, in particular, the signaling mechanisms by which two members of the LDLR gene family, apoE receptor-2 and VLDL receptor, control brain development, normal neuronal positioning, and neurotransmission in the adult brain.
Abbreviations: apoE, apolipoprotein E; apoER2, apoE receptor-2; APP, amyloid precursor protein; Dab1, Disabled-1; EGF, epidermal growth factor; GSK-3ß, glycogen synthase kinase 3ß; JIP, JNK-interacting protein; LDLR, LDL receptor; LRP, LDL receptor-related protein; LTP, long-term potentiation; NMDA, N-methyl-D-aspartate; PI3K, phosphatidylinositol-3-kinase; PI(4,5)P2, phosphatidylinositol-4,5-bisphosphate; PKB, protein kinase B; PTB, phosphotyrosine binding; QTL, quantitative trait locus; VLDLR, VLDL receptor
Supplementary key words apolipoprotein E receptor-2 • very low density lipoprotein receptor • Reelin
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