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Evaluation of the Polyketide GEX1A as a Potential Lead for Niemann‐Pick Type C Disease
Author(s) -
Granatosky Eve,
Pickering Jarred,
Stevens D.,
Taylor Richard
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.721.18
Subject(s) - context (archaeology) , natural product , disease , npc1 , niemann–pick disease, type c , polyketide , computational biology , biology , niemann–pick disease , bioinformatics , cancer research , gene , medicine , genetics , biochemistry , cell , pathology , biosynthesis , paleontology , endosome
Niemann‐Pick Type C (NPC) disease is a rare neurodegenerative disorder in which unesterified cholesterol accumulates in the lysosomes as a result of a mutation in either the NPC1 or NPC2 gene. Our efforts to identify a novel treatment for NPC disease are focused on the polyketide natural product GEX1A, derived from Streptomyces chromofuscus . We have observed that GEX1A is capable of improving cholesterol trafficking in NPC cells similar to other small molecules currently under investigation for the treatment of NPC disease, however our recent work suggests that GEX1A may exert its activity through a unique mode of action. Based on these findings, we aim to study the therapeutic potential and biological target of GEX1A. Here we highlight our multidisciplinary approach to accessing GEX1A and analogues and our studies of GEX1A's biological activity in the context of NPC disease.