Membrane domains as new drug targets

Our understanding of the plasma membrane of eukaryotic cells has undergone a profound change over the past 40 years. It is now well-understood that at the plasma membrane lipids and proteins are not randomly distributed, but are highly organized in discrete membrane domains with specific compositions. Well known examples of such domains include lipid rafts, tetraspanin-enriched microdomains, caveolae and cortical actin-dependent membrane compartments. This clustering and segregation of specific proteins and bioactive lipids control their function and allow for localized recruitment of signaling molecules. In fact, membrane domains act as dedicated platforms for a whole range of cellular functions, such as cell proliferation, adhesion, migration, and intracellular trafficking. By definition, this makes membrane domains appealing targets for drug treatment, which has sprouted in numerous research efforts to identify and characterize drugs that selectively target membrane domains. These drugs, that include well-known compounds such as the vaccine adjuvants aluminum and cholera toxin, may employ membrane domains for their cellular entry, or for triggering localized cellular signaling. Alternatively, these drugs may block or promote cellular functions by inducing, stabilizing, or disrupting the integrity or structure of these membrane domains, such as statins that are clinically used for treatment of cardiovascular disease and lipid disorders.
Goal of this Review Topic is to provide an overview of the latest insights in the rapidly developing field: the pharmaceutical potential of membrane domains. This overview should include a broad diversity of research areas ranging from biophysics, biochemistry, cell biology to pharmacology, but with a focus on drugs that function by selectively targeting membrane domains. Here, we aim to cover targeting strategies for a wide range of diseases and pathologies, including, but not limited to, cancer, infection, neuronal disorders, and cardiovascular disease.. For each of these drugs, we intend to discuss the molecular mechanisms underlying (i) their capacity to be selectively targeted towards membrane domains, and (ii) their pharmacological functions.
Together, we believe our Review Topic will provide an exciting overview of the various targeting and effector strategies of drugs that selectively target membrane domains. This synergistic overview will bring together previously detached research fields and disciplines. Given the increasing appreciation of the fundamental importance of membrane domains in cellular function, this overview will foster the development or optimization of new pharmaceutical strategies for a wide range of human diseases and disorders.