Methods and Compositions for Reducing Amyloid Beta Levels
AssigneeThe J. David Gladstone Institutes
InventorsLi Gan, Lennart Mucke, Erik Roberson, Sarah Mueller-Steiner
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Abstract
The present invention provides a method of increasing cathepsin B-induced cleavage of amyloid-β (Aβ) peptide in a cell or tissue, the method generally involving contacting the cell or tissue with an agent that increases the level of cathepsin B in the cell or tissue. The present invention further provides variant cathepsin B polypeptides that are resistant to inhibition by a cysteine protease inhibitor; as well as nucleic acids encoding the variants, and host cells comprising the nucleic acids.
Claims23
A method of increasing cathepsin B-induced cleavage of amyloid-β (Aβ) peptide in a neuron or a glial cell, the method comprising contacting the neuron or the glial cell with an agent that increases the level of cathepsin B-induced cleavage of Aβ in the neuron or the glial cell, wherein the agent is a non-steroidal anti-inflammatory agent.
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A method of reducing oligomeric amyloid beta protein aggregates in a tissue, the method comprising contacting the tissue with an agent that increases the level of cathepsin B activity produced by a cell in the tissue, wherein the increased level of cathepsin B results in a reduced level of oligomeric amyloid beta protein aggregates in the tissue.
A variant cathepsin B polypeptide, wherein said variant differs from native cathepsin B polypeptide by comprising an amino acid sequence alteration that provides for reduced inhibition by a cysteine protease inhibitor.
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Dependencies are inferred from the claim text.