Method of inhibiting tau phosphorylation
A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35 - 40.
1 . A method of inhibiting hyperphosphorylation of a tau protein in a patient, wherein the method comprises administering a compound of the structure:
or a pharmaceutically acceptable salt and/or solvate thereof to the patient.
2 . The method of claim 1 , wherein the patient has a phosphorylated tau protein at S 202 , T 231 , or T 181 .
3 . The method of claim 1 , wherein the method inhibits the hyperphosphorylation of a tau proteins at S 202 , T 231 , or T 181 .
4 . The method of claim 2 , wherein the method reduces the level of phosphorylation at S 202 , T 231 , or T 181 by at least 50%.
5 . The method of claim 1 , wherein the patient has a tau-containing neurofibrillary tangle (NFT).
6 . The method of claim 1 , wherein the method reduces formation of a tau-containing neurofibrillary tangle (NFT) in the patient's brain.
7 . The method of claim 1 , wherein the patient has a neuritic plaque.
8 . The method of claim 1 , wherein the method reduces formation of a neuritic plaque in the patient's brain.
9 . The method of claim 1 , wherein the compound is:
or pharmaceutically acceptable salt and/or solvate thereof.
10 . The method of claim 1 , wherein the compound is:
or pharmaceutically acceptable salt and/or solvate thereof.
11 . The method of claim 1 , wherein the compound is not a salt or solvate.
12 . The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt.
13 . The method of claim 1 , wherein the compound is a pharmaceutically acceptable solvate.
14 . The method of claim 1 , wherein the compound is administered orally.
15 . The method of claim 1 , wherein the compound is administered daily.
16 . The method of claim 1 , wherein the compound is administered once or twice daily.
17 . A method of inhibiting Aβ-induced α7nAChR-mediated signaling in a patient, wherein the method comprises administering a compound of the structure:
or a pharmaceutically acceptable salt and/or solvate thereof to the patient.
18 . The method of claim 17 , wherein the patient has a phosphorylated tau protein at S 202 , T 231 , or T 181 .
19 . A method of inhibiting interaction of Aβ with α7nAChR in a patient, wherein the method comprises administering a compound of the structure:
or a pharmaceutically acceptable salt and/or solvate thereof to the patient.
20 . The method of claim 19 , wherein the patient has a phosphorylated tau protein at S 202 , T 231 , or T 181 .