Identification of Modulators of Autophagy

Abstract

Methods for identifying compounds that inhibit or stimulate the autophagy pathway are described. Devices for detecting the expression of autophagy-related genes and kits for assaying the expression of autophagy-related genes are also described. Also described are methods for identifying individuals susceptible to or afflicted with a disease state associated with an autophagy pathway defect.

What is claimed is: 
     
         1 . A method for identifying compounds that inhibit or stimulate the autophagy pathway for treatment of a disease state associated with an autophagy pathway defect, comprising measuring the effect of one or more test compounds on the inhibition or stimulation of a product of one or more of the genes or gene fragments identified in Table 3 or Table 4. 
     
     
         2 . A method for identifying individuals susceptible to or afflicted with a disease state associated with an autophagy pathway defect, comprising testing a biological sample from an individual for a characteristic of one or more polypeptides produced by expression of one or more of the genes or gene fragments identified in Table 3 or Table 4 that is indicative of said disease state, wherein said characteristic is selected from the presence of at least one of said polypeptides, the absence of at least one of said polypeptides, an elevated level of at least one of said polypeptides, a reduced level of at least one of said polypeptides and, for two or more of said polypeptides, combinations thereof. 
     
     
         3 . A device for detecting the expression of a plurality of autophagy-related genes associated with an autophagy pathway defect, said device comprising a substrate to which is affixed at known locations a plurality of probes, wherein the probes comprise:
 a) a plurality of oligonucleotides or polynucleotides, each of which specifically binds to a different sequence selected from any of the sequences identified in Table 3 or Table 4 or fragments thereof; or   b) a plurality of polypeptide binding agents, each of which specifically binds to a different polypeptide or fragment thereof produced by expression of a gene or gene fragment comprising any of the sequences identified in Table 3 or Table 4 or fragments thereof.   
     
     
         4 . A kit for assaying the expression of autophagy-related genes associated with an autophagy pathway defect, comprising at least one container and a collection of two or more probes, wherein the probes comprise:
 a) oligonucleotides or polynucleotides that specifically bind to two or more genes or gene fragments comprising any of the sequences identified in Table 3 or Table 4, or fragments thereof; or   b) polypeptide binding agents that specifically bind to polypeptides produced by expression of two or more genes or gene fragments comprising any of the sequences identified in Table 3 or Table 4, or fragments thereof.