A high-throughput assay platform to discover small molecule activators of the phospholipase PLC-γ2 to treat Alzheimer's disease.

ABSTRACT: A naturally occurring missense variant of the phospholipase C isozyme, PLC-γ2, harboring a single substitution (P522R) protects against several neurodegenerative diseases, including Alzheimer's disease. The phospholipase activity of PLC-γ2 (P522R) is slightly elevated relative to its WT counterpart, and the general consensus is that this increased activity in microglia confers protection against neurodegeneration. In order to phenocopy this protection, we have developed a high-throughput assay to identify small molecule activators of PLC-γ2. The assay takes advantage of the fluorescent reporter, XY-69, embedded in lipid vesicles to readout the allosteric activation of PLC-γ2. The assay is highly reproducible and capable of identifying compounds with a large range of efficacies. A series of

SUBMITTER: Carr AJ 

PROVIDER: S-EPMC12131191 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature