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Cisd2 haploinsufficiency: A driving force for hepatocellular carcinoma

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Article: e1441627 | Received 11 Jan 2018, Accepted 15 Jan 2018, Published online: 13 Mar 2018

Figures & data

Figure 1. CISD2 as a potential therapeutic drug target for the treatment of NAFLD and NASH, and the prevention of HCC. A, In mice, CDGSH iron sulfur domain 2 (Cisd2) haploinsufficiency impairs sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 isoform b (Serca2b) activity and disrupts Ca2+ homeostasis leading to non-alcoholic fatty liver disease (NAFLD). While obesity impairs Serca2b activity via a decrease in Serca2b protein level. B, In human, CISD2 and SERCA2b are both possible drug targets for the treatment of NAFLD and the prevention of hepatocellular carcinoma (HCC). In addition to directly target SERCA2b, CISD2 activators may have the potential to treat NAFLD indirectly by enhancing SERCA2b activity through an increase in CISD2 protein level. ER, endoplasmic reticulum; HBV, hepatitis B virus; HFD, high fat diet; NASH, nonalcoholic steatohepatitis.

Figure 1. CISD2 as a potential therapeutic drug target for the treatment of NAFLD and NASH, and the prevention of HCC. A, In mice, CDGSH iron sulfur domain 2 (Cisd2) haploinsufficiency impairs sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 isoform b (Serca2b) activity and disrupts Ca2+ homeostasis leading to non-alcoholic fatty liver disease (NAFLD). While obesity impairs Serca2b activity via a decrease in Serca2b protein level. B, In human, CISD2 and SERCA2b are both possible drug targets for the treatment of NAFLD and the prevention of hepatocellular carcinoma (HCC). In addition to directly target SERCA2b, CISD2 activators may have the potential to treat NAFLD indirectly by enhancing SERCA2b activity through an increase in CISD2 protein level. ER, endoplasmic reticulum; HBV, hepatitis B virus; HFD, high fat diet; NASH, nonalcoholic steatohepatitis.