Linked Life Data

16266282

Source:http://linkedlifedata.com/resource/pubmed/id/16266282

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-11-3
pubmed:abstractText
This review will focus primarily on the role of the low density lipoprotein receptor-related protein (LRP-1) in neuronal synapse formation and function in Alzheimer's Disease (AD). We review the role that its ligands may have in cognition or AD: apolipoprotein E (ApoE), alpha2-macroglobulin, Transforming Growth Factor-Beta (TGFbeta, Tissue Plasminogen Activator (tPA), insulin growth factor binding protein-3 (IGFBP-3), which all bind LRP-1 and apolipoprotein J (ApoJ), which is a ligand for LRP-2. After reviewing its role as a signaling receptor, we discuss the connection between LRP and the NMDA glutamate receptor via the post synaptic density 95 (PSD-95) neuronal scaffold protein and the implications it may have for memory and cognition. Finally, we discuss the evidence supporting a role for LRP in AD. Although the evidence for LRP as a genetic risk factor is weak, many of its ligands impose genetic risk, and have been implicated in AD pathogenic cascades. We discuss the role of LRP in amyloid precursor protein (APP) processing and production of beta-amyloid (Abeta. We identify LRP ligands that accelerate aggregation of toxic Abeta species. LRP mediates crucial pathways in AD pathogenesis such as Abeta clearance, Abeta uptake, intraneuronal Abeta accumulation and Abeta-associated neuron death. Interestingly, the TGFbeta -V receptor is LRP-1. Data show that one critical ligand TGFbeta2, associated with neurodegeneration in amyloid diseases, induces LRP expression in PC12 cells. Data from rodent infusion models demonstrate the impact of TGFbeta2 in modifying Abeta- induced Long Term Potentiation (LTP) responses, presynaptic proteins, lipid peroxidation, gliosis and staining for neuronal nuclei. The evidence supports a complex and significant role of LRP in cognition and AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1568-007X
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
469-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Low density lipoprotein receptor-related proteins (LRPs), Alzheimer's and cognition.
pubmed:affiliation
University of California, Los Angeles, Department of Medicine, and the Veterans Administration Greater Los Angeles Healthcare System, Sepulveda 91343, USA. marni@ucla.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, N.I.H., Extramural