Lipid rafts as a therapeutic target.

Dmitri Sviridov; Nigora Mukhamedova; Yury I Miller
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 (iRafts) and cluster of apoptotic signaling molecule-enriched rafts (CASMERs). The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, liver X receptor (LXR) agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apolipoprotein A-I binding protein (AIBP). 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.
ISSN 1539-7262
Published 23 Mar 2020
DOI 10.1194/jlr.TR120000658
Type Journal Article