Future therapeutic targets for the treatment and prevention of cholesterol gallstones

Eur J Pharmacol. 2015 Oct 15:765:366-74. doi: 10.1016/j.ejphar.2015.08.045. Epub 2015 Sep 7.

Abstract

The formation of cholesterol gallstones involves very complex imbalances, such as alterations in the secretion of biliary lipids (which involves the ABCG5, ABCG8, ABCB4 and ABCB11 transporters), biochemical and immunological reactions in the gallbladder that produce biliary sludge (mucins), physicochemical changes in the structure of cholesterol (crystallization), alterations in gallbladder motility, changes in the intestinal absorption of cholesterol (ABCG5/8 transporters and Niemann-Pick C1L1 protein) and alterations in small intestine motility. Some of these proteins have been studied at the clinical and experimental levels, but more research is required. In this review, we discuss the results of studies on some molecules involved in the pathophysiology of gallstones that may be future therapeutic targets to prevent the development of this disease, and possible sites for treatment based mainly on the absorption of intestinal cholesterol (Niemann-Pick C1L1 and ABCG5/8 proteins).

Keywords: Cholesterol; Gallstones; Pathophysiology; Therapeutic target.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Bile / drug effects
  • Bile / metabolism
  • Cholesterol / metabolism*
  • Drug Delivery Systems / methods*
  • Forecasting
  • Gallstones / diagnosis
  • Gallstones / drug therapy*
  • Gallstones / metabolism*
  • Humans
  • Membrane Transport Proteins / metabolism
  • Treatment Outcome

Substances

  • ATP-Binding Cassette Transporters
  • Anticholesteremic Agents
  • Membrane Transport Proteins
  • Cholesterol