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Visual and Microscopic Evaluation of Streptomyces Developmental Mutants
Published on: September 12, 2018
GEX1A, a Polyketide from Streptomyces chromofuscus, Corrects the Cellular Defects Associated with Niemann-Pick Type
Eve A Granatosky1, Nina DiPrimio2, Jarred R E Pickering1
1Department of Chemistry and Biochemistry , University of Notre Dame , Notre Dame , Indiana 46556 , United States.
Abstract:
We report the first evidence of GEX1A, a polyketide known to modulate alternative pre-mRNA splicing, as a potential treatment for Niemann-Pick type C disease. GEX1A was isolated from its producing organism, Streptomyces chromofuscus, and screened in NPC1 mutant cells alongside several semisynthetic analogues. We found that GEX1A and analogues are capable of restoring cholesterol trafficking in NPC1 mutant fibroblasts, as well as altering the expression of NPC1 isoforms detected by Western blot. These results, along with the compound's favorable pharmacokinetic properties, highlight the potential of spliceosome-targeting scaffolds such as GEX1A for the treatment of genetic diseases.
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