METHODS FOR DIAGNOSING AND TREATING ALZHEIMER'S DISEASE (AD) USING THE MOLECULES THAT STABILIZE INTRACELLULAR CALCIUM (Ca2+) RELEASE

Abstract

The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed.

What is claimed is: 
     
         1 . A method of screening compounds to identify test compounds or agents that modulate expression of a target gene, gene variant or fragment thereof that is expressed in a cell, said target gene selected from genes encoding FKBP1a and FKBP1b, junctophilin 3, junctophilin 4, calmodulin 3 and InsP3Rs, comprising the steps of:
 (1) exposing the cell to the test compound or agent; and   (2) selecting the test compounds or agents that modulate the expression of the target gene, gene variant or fragment thereof relative to a control.   
     
     
         2 . The method of  claim 1  wherein the test compounds or agents are selected from peptides, peptidomimetics, peptoids, small molecules and large molecules. 
     
     
         3 . The method of  claim 1  wherein the target gene is selected from FKBP1a and FKBP1b, FKBP1a and FKBP1b variants and fragments thereof. 
     
     
         4 . The method of  claim 3  wherein the test compounds or agents enhance the expression of the target gene, target gene variant or fragment thereof. 
     
     
         5 . A method for screening test compounds or agents to identify compounds agents that modulate the activity or expression of a target protein selected from FKBP1a, FKBP1b, junctophilin 3, junctophilin 4, calmodulin 3 and InsP3Rs comprising the steps of:
 (1) exposing the target protein to a test compound in the presence of a substrate for the target protein; and   (2) selecting the test compounds that alter the interaction of the target protein with the substrate or enhance or inhibit the activity of the target protein.   
     
     
         6 . The method of  claim 5  wherein the test compounds or agents are selected from peptides, peptidomimetics, peptoids, small molecules and large molecules 
     
     
         7 . The method of  claim 5  wherein the target protein is FKBP1b or FKBP1a. 
     
     
         8 . The method of  claim 7 , further comprising testing the compounds of step (2) to determine whether they alter the cognitive function of a test subject. 
     
     
         9 . The method of  claim 5 , further comprising exposing the compounds of step (2) to neural cells and measuring calcium release stability in said neural cells.