YEAST-BASED METHODS OF IDENTIFYING NUCLEIC ACIDS AND COMPOUNDS FOR TREATING NEURODEGENERATIVE DISEASES

摘要

The disclosure encompasses methods for the screening of small molecules or nucleic acids that may reverse the inhibition of growth of the unicellular yeast Schizosaccharomyces pombe by rotenone. The use of a yeast as the screening target allows for the high-throughput screening of small molecule and nucleic acid libraries for candidates that may then be screened in animal models as therapeutic agents for the treatment of neurodegenerative diseases. The plant-derived isoflavonoid, rotenone, while only moderately inhibitory to S. pombe cell growth on complex rich medium, is highly inhibitory to growth on synthetic minimal medium. S. pombe cells carrying a deletion in the gene pmk1 are hypersensitive to rotenone. S. pombe, therefore, provides a model for elucidating complex 1-independent targets of rotenone, and can serve as a screening tool for identifying compounds or oligonucleotides potentially able to reverse the effects of rotenone or Parkinson's disease in animal or human subjects.