Lipid rafts as a therapeutic target

J Lipid Res. 2020 May;61(5):687-695. doi: 10.1194/jlr.TR120000658. Epub 2020 Mar 23.

Abstract

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.jlr;61/5/687/F1F1f1.

Keywords: cancer; cholesterol; cluster of apoptotic signaling molecule-enriched rafts; inflammation; membrane lipids; metabolism; neurodegeneration; sphingolipid.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Microdomains / drug effects*
  • Membrane Microdomains / metabolism
  • Molecular Targeted Therapy / methods*