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.
Claims11
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 a recombinant expression vector comprising a nucleotide sequence that encodes cathepsin B, wherein the encoded cathepsin B comprises an amino acid sequence at least 95% identical to amino acids 8 1-328 of SEQ ID NO:2,
- wherein the recombinant expression vector enters the neuron or the glial cell,
- wherein cathepsin B encoded by the recombinant expression vector is produced in the neuron or the glial cell at a higher level than in a neuron or a glial cell not contacted with the recombinant expression vector, and
- wherein the encoded cathepsin B cleaves Aβ in the neuron or the glial cell.
Dependencies are inferred from the claim text.