Compositions and Methods for Suppression of Amyloid Plaque Formation Associated with Neurodegenerative Disorders

摘要

The invention provides a method for reducing or inhibiting net beta-amyloid peptide production and amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 polypeptide, wherein the netrin-1 polypeptide comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits Abeta peptide production. A netrin-1 polypeptide has an amino acid sequence sufficient for specific binding of the netrin-1 polypeptide to the APP protein. A netrin-1 polypeptide can mimic netrin-1-mediated signal transduction by altering the localization, protein-protein binding and/or enzymatic activity of an intracellular protein involved in an APP signal pathway. The invention also provides a method for reducing or inhibiting amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 therapeutic, wherein the netrin-1 therapeutic comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits Abeta peptide production.