Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
1997-03-12
2001-07-31
Caputa, Anthony C. (Department: 1645)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C930S010000
Reexamination Certificate
active
06268479
ABSTRACT:
Throughout this application, various references are referred to by numbers within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims, in numerical order corresponding to the numbers within parentheses.
BACKGROUND OF THE INVENTION
Processing of the beta-amyloid precursor protein (APP) leads to a range of proteolyzed forms (1-6), some of which assemble into beta-amyloid fibrils and are cytotoxic. &bgr;-amyloid moieties, such as amyloid-beta peptide (A&bgr;), are closely associated with neuronal dysfunction and death in Alzheimer's disease (AD). Increased expression of amyloid-beta peptide is linked to mutations in APP (6-10) and in presenilins (11-13), both of which occur in familial AD. The mechanisms underlying the cellular stress phenotype brought about in cells by amyloid-beta peptide-derived peptides are likely related to the neurotoxicity leading to dementia. Most attention has been focussed on mechanisms by which extracellular amyloid-beta peptide exerts its effects on cells, since the most visible accumulations of amyloid-beta peptide occur extracellularly in plaques. Amyloid-beta peptide aggregates, especially those that assemble into fibrils, can be cytotoxic by nonspecifically disturbing the integrity of cell membranes, and by elaborating reactive oxygen intermediates (14-15), thereby resulting in elevation of cytosolic calcium eventually followed by cell death (15-16). Cell surface receptors for amyloid-beta peptide (17-19) could also activate signal transduction mechanisms. The receptor RAGE, an immunoglobulin superfamily molecule, is one such neuronal cell surface docking site which binds amyloid-beta peptide and facilitates amyloid-beta peptide-mediated cellular oxidant stress (19).
SUMMARY OF THE INVENTION
The present invention provides an isolated nucleic acid encoding an endoplasmic reticulum associated amyloid-beta peptide binding (ERAB) polypeptide. The ERAB polypeptide may comprise human ERAB polypeptide. The present invention provides a purified ERAB polypeptide, as well as a method for treating a neurodegenerative condition in a subject which comprises administering to the subject an agent in amount effective to inhibit ERAB polypeptide binding to amyloid-beta peptide so as to thereby treat the neurodegenerative condition.
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Stern David M.
Yan Shi Du
Caputa Anthony C.
Cooper & Dunham LLP
Hayes Robert C.
The Trustees of Columbia University in the City of New York
White John P.
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