Modulation of autophagy for the treatment of liver diseases

Abstract

Introduction: Autophagy is a cellular process essential for survival and homeostasis that confers cellular protection toward a wide range of deleterious stimuli. It has a highly complex regulation with several autophagic proteins also belonging to other main signaling pathways as cell proliferation or apoptosis. In addition, autophagy has an important role in cell metabolism. Interest in the study of this process is rapidly rising and, in the past few years, autophagy has been implicated in a variety of hepatic diseases.

Areas covered: The review covers the research and investigational use of pharmacological strategies that modify autophagy in the treatment of liver diseases. Autophagy modulation in steatosis, steatohepatitis, viral hepatitis, fibrogenesis, cirrhosis, hepatocellular carcinoma and ischemia/reperfusion injury will be described, critically analyzed and discussed. Papers included in the present manuscript were selected from the PubMed search: liver + (macro)autophagy + each of the pathologies described above.

Expert opinion: The complexity of autophagy creates significant controversy on the potential of its pharmacological modulation. A major requirement for drugs regulating autophagy in the treatment of liver diseases is that these should be liver-specific; moreover, they should primarily target one specific hepatic cell type.

Keywords::

• chloroquine
• cirrhosis
• hepatic
• ischemia
• non-alcoholic fatty liver disease

Declaration of interest

The authors were supported by the Instituto de Salud Carlos III – Ministerio de Economía y Competitividad (FIS PI11/00235, FIS PS09/01261, FIS PI13/00341). J Gracia-Sancho has a Ramón y Cajal contract from the Ministerio de Economía y Competitividad. S Guixé-Muntet has a fellowship from the Societat Catalana de Transplantament and D Hide from Ministerio de Educación (FPU2010-3090). Ciberehd is funded by the Instituto de Salud Carlos III. J Bosch is also a consultant for Gilead, Chiasma, Ono-UK, Conatus Pharmaceuticals, Almirall, Exallenz and Bayer Pharmaceuticals. 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.

Notes

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