Methods and compositions for treating neurodegenerative disorders and alzheimer's disease and improving normal memory
View Patent ↗The disclosure relates generally to neurodegenerative disorders and more specifically to a group of presenilin/G-protein/c-src binding polypeptides and methods of use for modulating signaling and progression of Alzheimer's disease.
1. A pharmaceutical composition comprising an isolated polypeptide in a pharmaceutically acceptable carrier, wherein the polypeptide consists essentially of an amino acid sequence from the N-terminal fragment of PS-1 (SEQ ID NO:2), wherein the fragment is selected from the group consisting of:
(i) DEEEDEEL (SEQ ID NO:5),
(ii) SEQ ID NO:5 having 1-10 additional amino acids at either the N- and/or C-terminal end(s),
(iii) RRSLGHPEPLSNGRPQGNSRQWEQDEEEDEELTLKYGAK (SEQ ID NO:7),
(iv) a polypeptide that is at least 85% identical to SEQ ID NO:7 having 1-5 conservative amino acid substitutions,
(v) a sequence of (iii) or (iv) having 1-10 additional amino acids at the N- and/or C-terminal end(s),
(vi) DEEEDELTLKYGAK (SEQ ID NO:17),
(vii) SEQ ID NO:17 having 1-2 conservative amino acid substitutions,
(viii) a sequence of (vi) or (vii) having 1-10 additional amino acids at the N- or C-terminus,
(ix) any of the foregoing polypeptides comprising an unnatural amino acid or D-amino acid, and
(x) combinations of any of the foregoing,
wherein the isolated polypeptide inhibits production of Aβ in a cell.
2. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence DEEEDEEL (SEQ ID NO:5).
3. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence RRSLGHPEPLSNGRP (SEQ ID NO:6).
4. The pharmaceutical composition of claim 1 , wherein the polypeptide comprises an unnatural amino acid or D-amino acid.
5. The pharmaceutical composition of claim 1 , wherein the composition includes a sterile aqueous solution.
6. The pharmaceutical composition of claim 1 , wherein the composition is in a solvent-free form.
7. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence of DEEEDEEL (SEQ ID NO:5) having 1-10 additional amino acids at either the N- and/or C-terminal end(s).
8. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence RRSLGHPEPLSNGRPQGNSRQWEQDEEEDEELTLKYGAK (SEQ ID NO:7).
9. The pharmaceutical composition of claim 8 , wherein the polypeptide comprises an unnatural amino acid or D-amino acid.
10. The pharmaceutical composition of claim 8 , wherein the composition includes a sterile aqueous solution.
11. The pharmaceutical composition of claim 8 , wherein the composition is in a solvent-free form.
12. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence of RRSLGHPEPLSNGRPQGNSRQWEQDEEEDEELTLKYGAK (SEQ ID NO:7) having 1-10 additional amino acids at either the N- and/or C-terminal end(s).
13. The pharmaceutical composition of claim 1 , wherein the polypeptide is at least 85% identical to RRSLGHPEPLSNGRPQGNSRQWEQDEEEDEELTLKYGAK (SEQ ID NO:7) having 1-5 conservative amino acid substitutions.
14. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence of DEEEDELTLKYGAK (SEQ ID NO:17).
15. The pharmaceutical composition of claim 14 , wherein the polypeptide comprises an unnatural amino acid or D-amino acid.
16. The pharmaceutical composition of claim 14 , wherein the composition includes a sterile aqueous solution.
17. The pharmaceutical composition of claim 14 , wherein the composition is in a solvent-free form.
18. The pharmaceutical composition of claim 1 , wherein the polypeptide has the sequence of DEEEDELTLKYGAK (SEQ ID NO:17) having 1-10 additional amino acids at either the N- and/or C-terminal end(s).
19. The pharmaceutical composition of claim 1 , wherein the polypeptide is at least 85% identical to DEEEDELTLKYGAK (SEQ ID NO:17) having 1-2 conservative amino acid substitutions.