GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:17920016
| Citation |
Liu, Q, Zerbinatti, CV, Zhang, J, Hoe, HS, Wang, B, Cole, SL, Herz, J, Muglia, L and Bu, G (2007) Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 56:66-78 |
|---|---|
| Abstract |
Mutations in the amyloid precursor protein (APP) cause early-onset Alzheimer's disease (AD), but the only genetic risk factor for late-onset AD is the varepsilon4 allele of apolipoprotein E (apoE), a major cholesterol carrier. Using Cre-lox conditional knockout mice, we demonstrate that lipoprotein receptor LRP1 expression regulates apoE and cholesterol levels within the CNS. We also found that deletion of APP and its homolog APLP2, or components of the gamma-secretase complex, significantly enhanced the expression and function of LRP1, which was reversed by forced expression of the APP intracellular domain (AICD). We further show that AICD, together with Fe65 and Tip60, interacts with the LRP1 promoter and suppresses its transcription. Together, our findings support that the gamma-secretase cleavage of APP plays a central role in regulating apoE and cholesterol metabolism in the CNS via LRP1 and establish a biological linkage between APP and apoE, the two major genetic determinants of AD. |
| Links |
PubMed PMC2045076 Online version:10.1016/j.neuron.2007.08.008 |
| Keywords |
Amyloid Precursor Protein Secretases/metabolism; Amyloid beta-Protein Precursor/deficiency; Amyloid beta-Protein Precursor/physiology; Animals; Animals, Newborn; Apolipoproteins E/metabolism; Brain/metabolism; Cell Line, Transformed; Cholesterol/metabolism; Chromatin Immunoprecipitation; Cricetinae; Cytidine Deaminase/metabolism; Enzyme-Linked Immunosorbent Assay/methods; Gene Expression Regulation, Developmental/genetics; Gene Expression Regulation, Developmental/physiology; Histone Acetyltransferases/pharmacology; Humans; Mice; Mice, Knockout; Nerve Tissue Proteins/pharmacology; Nuclear Proteins/pharmacology; RNA, Messenger/biosynthesis; Receptors, LDL/deficiency; Receptors, LDL/physiology; Reverse Transcriptase Polymerase Chain Reaction/methods; Transfection/methods; Tumor Suppressor Proteins/deficiency; Tumor Suppressor Proteins/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| edit table |
See also
References
See Help:References for how to manage references in GONUTS.
