Description of Invention: Alzheimer's disease is the most important dementing illness in the United States because of its high prevalence. Five to ten percent of the United States population 65 years and older are afflicted with the disease. In 1990 there were approximately 4 million individuals with Alzheimer's, and this number is expected to reach 14 million by the year 2050. It is the fourth leading cause of death for adults, resulting in more than 100,000 deaths annually. Amyloid beta has been identified as playing an important role in the neurodegeneration of Alzheimer's disease. However, the mechanism by which this occurred was unknown, but has been postulated to be either direct or indirect through an induction of inflammatory responses.
The NIH announces the identification of the 7-transmembrane, G-protein-coupled receptor, FPRL-1, in the cellular uptake and fibrillar aggregation of amyloid beta-beta (Abeta-beta) peptides. The Abeta-beta peptides use the FPRL-1 receptor to attract and activate human monocytes and mouse microglial cells (publications referenced below), and have been identified as a principal component of the amyloid plaques associated with Alzheimer’s disease. In addition, the known anti-inflammatory drug, Colchicine, has been shown to inhibit the FPRL1 activation by amyloid and the internalization of FPRL1/amyloid beta complexes.
Inventors: No Inventor Information Available.
Patent Status: HHS, Reference No. E-336-2001/0
Y Le, W Gong, L Tiffany, A Tumanov, S Nedospasov, W Shen, NM Dunlop,
J-L Gao, PM Murphy, JJ Oppenheim, and JM Wang. Amyloid (beta)42 activates
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Tiffany, MC Lavigne, YH Cui, JM Wang, TL Leto, JL Gao, and PM Murphy.
Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide
receptor 2, a G protein-coupled receptor expressed in phagocytes and brain.
J Biol Chem. 2001 Jun 29;276(26):23645-23652. [ PubMed abs ]
Cui, Y Le, W Gong, P Proost, J Van Damme, WJ Murphy, and JM Wang.
Bacterial lipopolysaccharide selectively up-regulates the function of the
chemotactic peptide receptor formyl peptide receptor 2 in murine microglial
cells. J Immunol. 2002 Jan 1;168(1):434-442. [ PubMed abs ]
azawa., Z-X Yu, K Takeda, Y Le, W Gong, VJ Ferrans, JJ Oppenheim,
CC Li, and JM Wang. Beta amyloid peptide (Ab42) is internalized via the G-protein
coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB
J. 2001 Nov; 15(13):2454-2462. [ PubMed abs ]
ribarren, K Chen, J Hu, G Gong, EH Cho, S Lockett, B Uranchimeg, and
JM Wang. CpG-containing oligodeoxynucleotide promotes microglial the up-take
of amyloid beta 1-42 by up-regulating the expression of the G-protein coupled
receptor mFPR2. FASEB J. 2005 Dec;19(14):2032-2034. [ PubMed abs ]
hen, P Iribarren, J Hu, J Chen, G Gong, EH Cho, S Lockett, NM Dunlop,
and JM Wang. Activation of Toll-like receptor 2 on microglia promotes cell
uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem.
2006 Feb 10;281(6):3651-3659. [ PubMed abs ]
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Collaborative Research Opportunity: The National Cancer Institute, Laboratory of Molecular Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialized siRNA delivery development. Please contact Donna Bialozor at 301/846-5465 or firstname.lastname@example.org for more information.
Portfolios: Internal Medicine Internal Medicine - Therapeutics Central Nervous System Central Nervous System - Therapeutics