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 treating Alzheimer's disease in a patient, comprising administering to a patient having Alzheimer's disease a compound of the structure:
or a pharmaceutically acceptable salt and/or solvate thereof.
2 . The method of claim 1 , wherein the patient has an Alzheimer's disease symptom.
3 . The method of claim 1 , wherein the patient has been diagnosed as having Alzheimer's disease.
4 . The method of claim 1 , wherein the patient has a phosphorylated tau protein at S 202 , T 231 , or T 181 .
5 . The method of claim 4 , wherein the method reduces the level of phosphorylation at S 202 , T 231 , or T 181 by at least 50%.
6 . The method of claim 1 , wherein the method inhibits hyperphosphorylation of a tau protein at S 202 , T 231 , or T 181 .
7 . The method of claim 1 , wherein the patient has a tau-containing neurofibrillary tangle (NFT).
8 . The method of claim 1 , wherein the method reduces formation of a tau-containing neurofibrillary tangle (NFT) in the Alzheimer's disease patient's brain.
9 . The method of claim 1 , wherein the method inhibits Aβ 42 -induced formation of a tau-containing neurofibrillary tangle (NFT).
10 . The method of claim 1 , wherein the patient has a neuritic plaque.
11 . The method of claim 1 , wherein the method reduces formation of a neuritic plaque in the Alzheimer's disease patient's brain.
12 . The method of claim 1 , wherein the method inhibits Aβ 42 -induced formation of a neuritic plaque.
13 . The method of claim 1 , wherein the method reduces inflammation in Alzheimer's disease patient's brain.
14 . The method of claim 1 , wherein the method helps preserve the Alzheimer's disease patient's memory.
15 . The method of claim 1 , wherein the method provides cognitive recovery or mitigates further cognitive degeneration in the Alzheimer's disease patient.
16 . The method of claim 1 , wherein the method inhibits interaction of Aβ with α7nAChR.
17 . The method of claim 1 , wherein the method inhibits Filamin A (FLNA)-mediated signaling.
18 . The method of claim 17 , wherein the FLNA-mediated signaling is associated with an impairment in α-7 nicotinic acetylcholine receptor (α7nAChR) function.
19 . The method of claim 18 , wherein the impairment in α7nAChR function is induced by Aβ 42 .
20 . The method of claim 17 , wherein the FLNA-mediated signaling is associated with toll-like receptor-4 (TLR4) activation.
21 . The method of claim 20 , wherein TLR4 is induced by Aβ 42 .
22 . The method of claim 21 , wherein the method inhibits Aβ 42 -induced inflammatory cytokine production.
23 . The method of claim 1 , wherein the method inhibits Aβ-induced α7nAChR-mediated signaling.
24 . The method of claim 1 , wherein the compound is:
or pharmaceutically acceptable salt and/or solvate thereof.
25 . The method of claim 1 , wherein the compound is:
or pharmaceutically acceptable salt and/or solvate thereof.
26 . The method of claim 1 , wherein the compound is not a salt or solvate.
27 . The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt.
28 . The method of claim 1 , wherein the compound is a pharmaceutically acceptable solvate.
29 . The method of claim 1 , wherein the compound is administered orally.
30 . The method of claim 1 , wherein the compound is administered daily; optionally wherein the compound is administered once or twice daily.