Neuroprotective Chemicals and Methods for Identifying and Using Same

Abstract

Provided herein are methods for identifying a compound having cell-protective (e.g., neuroprotective) activity. Compounds identified therefrom are also provided. These compounds can be used to treat various diseases, disorders, or conditions associated with, for example, unwanted cell death.

1 . A method for identifying a compound having cell-protective activity, comprising:
 incubating a test compound with a nicotinamide phosphoribosyltransferase (NAMPT); and   measuring an activity of the NAMPT;   wherein an increase in the activity of the NAMPT compared to a control that is not incubated with the test compound is indicative of cell-protective activity of the test compound.   
     
     
         2 . The method of  claim 1 , wherein in the incubating step, the NAMPT is recombinantly produced. 
     
     
         3 . The method of  claim 1 , wherein in the incubating step, the NAMPT is present at about 0.1 to about 10 μM, about 0.5 to about 5 μM, or about 1 μM. 
     
     
         4 . The method of  claim 1 , further comprising incubating the test compound with nicotinamide, phosphoribosylpyrophosphate, alcohol dehydrogenase, nicotinamide mononucleotide adenylyl-transferase, and an alcohol. 
     
     
         5 . The method of  claim 4 , wherein the alcohol is ethanol. 
     
     
         6 . The method of  claim 1 , wherein the measuring step comprises determining an amount of nicotinamide adenine dinucleotide reduced form (NADH) and/or nicotinamide mononucleotide (NMN). 
     
     
         7 . The method of  claim 6 , wherein the amount of NADH and/or NMN is measured by ultra violet light, mass spectrometry or fluorescence. 
     
     
         8 . The method of  claim 7 , wherein the amount of NADH is measured by optical density 340 nm. 
     
     
         9 . The method of  claim 6 , wherein an increase in the amount of NADH and/or NMN is indicative of increased NAMPT activity. 
     
     
         10 . The method of  claim 1 , wherein the test compound having said cell-protective activity is determined to bind and/or activate the NAMPT. 
     
     
         11 . The method of  claim 1 , wherein the cell-protective activity is neuroprotective activity which includes one or more of: promoting survival, health, integrity, growth, development and/or function of neurons, protecting neurons from cell death, apoptosis and/or degeneration, and/or stimulating neurogenesis.