Peptide compounds for suppressing inflammation
Provided herein are peptides that exhibit ApoE biological activity, as well as compositions and pharmaceutical formulations that include the peptides. The peptides, compositions, and methods disclosed herein have broad applications as they can be used to treat a broad spectrum of injury, diseases, disorders, and clinical indications.
1. A method of treating Alzheimer's disease in a human subject in need thereof, the method comprising administering to the subject a composition comprising an effective amount of a peptide of Formula I:
X1-X2-X3-X4-X5 (SEQ ID NO:1)
or a salt thereof, wherein
X1 is V;
X2 is S;
X3 is K or R;
X4 is K or R; and
X5 is R.
2. The method of claim 1 , wherein Formula I comprises VSRKR (SEQ ID NO:2), VSKRR (SEQ ID NO:3), or VSRRR (SEQ ID NO:4).
3. The method of claim 1 , wherein the peptide does not have primary polypeptide sequence identity with any region of 5 consecutive amino acids of human ApoE protein (SEQ ID NO:14).
4. The method of claim 1 , wherein the peptide does not have primary polypeptide sequence identity with any 5 consecutive amino acids from residue 130 to residue 150 of human ApoE protein (SEQ ID NO:14).
5. The method of claim 1 , wherein the peptide suppresses activation of microglial cells.
6. The method of claim 1 , wherein the peptide suppresses secretion of TNF-α by cultured microglial cells exposed to lipopolysaccharide.
7. The method of claim 1 , wherein the peptide suppresses secretion of nitric oxide by cultured microglial cells exposed to lipopolysaccharide.
8. The method of claim 1 , wherein the peptide binds a cell-surface ApoE receptor.
9. The method of claim 1 , wherein the peptide blocks NMDA receptor mediated excitotoxicity.
10. The method of claim 1 , wherein the administering the peptide is by an injection, inhalation, transdermal, intravenous, intranasal, intracranial, and/or intrathecal route.
11. The method of claim 1 , wherein said peptide is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
12. The method of claim 1 , wherein the administering the peptide is by an intravenous route.
13. The method of claim 1 , wherein the administering the peptide is by intravenous injection.
14. The method of claim 1 , wherein the effective amount of the peptide is at least about 0.1 mg/kg and less than about 25 mg/kg.
15. The method of claim 1 , wherein the peptide is N-terminal acetylated and/or C-terminal amidated.
16. The method of claim 1 , wherein the peptide is N-terminal acetylated and C-terminal amidated.