Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.

Schizophrenia is a chronic and severe mental disorder. It is currently treated with antipsychotic drugs (APD). However, APD's work only in a limited number of patients and may have cognition impairing side effects.

Advancing skin model development: A focus on a self-assembled, induced pluripotent stem cell-derived, xeno-free approach.

The demand for skin models as alternatives to animal testing has grown due to ethical concerns and the need for accurate substance evaluation. These alternatives, known as New Approach Methodologies (NAMs), are increasingly used for regulatory decisions. Current skin models from primary human cells often rely on bovine collagen, raising ethical issues.

Live-Cell Identification of Inhibitors of the Lipid Transfer Protein CERT Using Nanoluciferase Bioluminescence Resonance Energy Transfer (NanoBRET).

A BRET system is described, in which Nanoluciferase was fused to the lipid transfer protein CERT for efficient energy transfer to a Nile red-labeled ceramide, which is either directly bound to CERT or transported to the adjacent Golgi membrane. Bulk formation of sphingomyelin, a major plasma membrane component in mammals, is dependent on CERT-mediated transfer of its predecessor ceramide. CERT is considered a promising drug target but no direct cell-based methods exist to efficiently identify inhibitors.

Trifunctional sphingomyelin derivatives enable nanoscale resolution of sphingomyelin turnover in physiological and infection processes via expansion microscopy.

Sphingomyelin is a key molecule of sphingolipid metabolism, and its enzymatic breakdown is associated with various infectious diseases. Here, we introduce trifunctional sphingomyelin derivatives that enable the visualization of sphingomyelin distribution and sphingomyelinase activity in infection processes. We demonstrate this by determining the activity of a bacterial sphingomyelinase on the plasma membrane of host cells using a combination of Förster resonance energy transfer and expansion microscopy.