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LXR/RXR Activation as therapeutic approach to decrease amyloid secretion and prevent the development of Alzheimer's disease

Summary

Lead Inventors: Alan Tall, Tae-Wan Kim, Yu Sum Problem or Unmet Need:Formation of amyloid beta-peptide (Ab) plaques in the brain is the hallmark of Alzheimer's disease. Reversing or even halting the brain's deterioration requires effective treatments for preventing or reducing Ab plaque deposition. Amyloid-beta peptides are generated through sequential cleavage of APP by beta- and gamma- secretases. An alternative initial cleavage of APP by alpha-secretase precludes subsequent Ab formation. Regulators of APP processing could be possible drug targets for treating Alzheimer's disease.The technology utilizes the fact that beta-secretase is associated with cholesterol-rich plasma membrane lipid domains ("lipid rafts"). And cholesterol depletion reduces Ab deposition. The Liver-X receptor family (LXRs) plays a key role in regulating genes that control cholesterol efflux and membrane composition. Two major targets of LXR and RXR (retinoic acid receptors) regulation are ABCA1 and SCD, and the expression of these genes individually decreases the deposition of Ab. The invention shows that LXR activation and RXR activation via their respective ligands decreases Ab secretion in a neuroblastoma cell line The invention also shows that the reduction in Ab secretion is mediated by a decrease in both beta and gamma- secretase activities

Technology Benefits

Small-molecules type drugs can be used to activate the LXR/RXR regulatory pathways

Technology Application

A drug to treat Alzheimer's Disease A drug to prevent Alzheimer's Disease in risk populations

Detailed Technology Description

The technology utilizes the fact that beta-secretase is associated with cholesterol-rich plasma membrane lipid domains ("lipid rafts"). And cholesterol depletion reduces Ab deposition. The Liver-X receptor family (LXRs) pla...

*Abstract

None

*Inquiry

Peter Golikov Columbia Technology Ventures Tel: (212) 854-8444 Email: TechTransfer@columbia.edu

*IR

1351

*Principal Investigator

*Publications

Costet et. al, Retinoic acid receptor-mediated induction of ABCA1 in macrophages. Mol Cell Biol. 21:7756-66 2003. Wang and Tall, Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 23(7):1178-84 2003. Sun et. al, Stearoyl-CoA desaturase inhibits ATP-binding cassette transporter A1-mediated cholesterol efflux and modulates membrane domain structure. J Bio Chem 278(8) 5813-20 200.

*Web Links

USPTO: Patent pending

Country/Region

USA