Targeting endoplasmic reticulum stress in liver disease

ABSTRACT

Introduction: The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention.

Areas covered: This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention.

Expert Commentary: We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed.

KEYWORDS:

• Endoplasmic reticulum stress
• alcoholic liver disease
• nonalcoholic fatty liver disease
• drug-induced liver injury
• acute-on-chronic liver failure
• hepatocellular carcinoma
• therapeutic target

Financial & competing interests disclosure

This work was supported by grants from National Natural Science Foundation of China (81500665), Health Bureau of Zhejiang Province (2010KYB070), Research Foundation of Education Bureau of Zhejiang Province (Y201009942) and Project of New Century 551 Talent Nurturing in Wenzhou. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.