Publication Date:
2009-02-14
Description:
Deposition of the amyloid-beta peptide is a pathological hallmark of Alzheimer's disease. A high-throughput functional genomics screen identified G protein-coupled receptor 3 (GPR3), a constitutively active orphan G protein-coupled receptor, as a modulator of amyloid-beta production. Overexpression of GPR3 stimulated amyloid-beta production, whereas genetic ablation of GPR3 prevented accumulation of the amyloid-beta peptide in vitro and in an Alzheimer's disease mouse model. GPR3 expression led to increased formation and cell-surface localization of the mature gamma-secretase complex in the absence of an effect on Notch processing. GPR3 is highly expressed in areas of the normal human brain implicated in Alzheimer's disease and is elevated in the sporadic Alzheimer's disease brain. Thus, GPR3 represents a potential therapeutic target for the treatment of Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thathiah, Amantha -- Spittaels, Kurt -- Hoffmann, Marcel -- Staes, Mik -- Cohen, Adrian -- Horre, Katrien -- Vanbrabant, Mieke -- Coun, Frea -- Baekelandt, Veerle -- Delacourte, Andre -- Fischer, David F -- Pollet, Dirk -- De Strooper, Bart -- Merchiers, Pascal -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):946-51. doi: 10.1126/science.1160649.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Developmental Genetics, Vlaams Institute for Biotechnology, Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213921" target="_blank"〉PubMed〈/a〉
Keywords:
Adult
;
Aged
;
Amyloid Precursor Protein Secretases/metabolism
;
Amyloid beta-Peptides/*biosynthesis
;
Animals
;
Cell Line
;
Cell Line, Tumor
;
Cells, Cultured
;
Female
;
Humans
;
Male
;
Mice
;
Middle Aged
;
Neurons/*metabolism
;
Protein Structure, Tertiary
;
Receptors, G-Protein-Coupled/*metabolism
;
Receptors, Notch/metabolism
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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