LRP and Alzheimer's disease.

Abstract

The low-density lipoprotein receptor (LDLR)-related protein, LRP, is a unique member of the LDLR family. Frequently referred to as a scavenger receptor, LRP is a large transmembrane endocytic receptor that can bind and internalize many functionally distinct ligands. Besides its role as a cargo-receptor, LRP has also been implicated in many signaling pathways. LRP knockout mice die at early embryonic age, which strongly suggests that LRP's functions are essential for normal development. Within the CNS, LRP is highly expressed in neuronal cell bodies and dendritic processes. In vitro, neurite outgrowth is stimulated by apolipoprotein E (apoE)-containing lipoprotein particles via binding to LRP. ApoE is the major cholesterol transporter in the brain and human carriers of one or two copies of the e4 allele of apoE are at a higher risk of developing Alzheimer's disease (AD). LRP also binds the amyloid precursor protein (APP) and its proteolytic fragment, the amyloid-beta peptide (Abeta), which are major players in the pathogenesis of AD. Finally, LRP has been linked to AD by genetic evidence. In this review we discuss the potential mechanisms by which LRP can affect APP and Abeta metabolism, and therefore contribute to the pathogenesis of AD.

• Authors: Celina V Zerbinatti, Guojun Bu
• Journal: Reviews in the neurosciences (Rev Neurosci) Vol. 16 Issue 2 Pg. 123-35 ( 2005) ISSN: 0334-1763 [Print] Germany
• PMID: 15959937 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Amyloid beta-Protein Precursor
• Low Density Lipoprotein Receptor-Related Protein-1

Topics

• Alzheimer Disease (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Central Nervous System (metabolism)
• Humans
• Low Density Lipoprotein Receptor-Related Protein-1 (classification, metabolism)
• Models, Biological