14-3-3 protein eta

14-3-3 protein eta (YWHAH) is an adapter protein that regulates diverse signaling pathways through phosphorylation-dependent binding to partner proteins, particularly those containing phosphoserine or phosphothreonine motifs (UniProt: Q04917). It negatively modulates PDPK1 kinase activity and functions as a critical hub in cellular signal transduction. The protein is expressed broadly across tissues and participates in both general and specialized regulatory networks.

In the context of Alzheimer's Disease, 14-3-3 protein eta is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomic analysis using tandem mass tag labeling across subcellular fractions revealed a mean log2 fold-change of −1.12, indicating reduced abundance in the disease state. This downregulation may impair signaling regulation and protein-protein interactions dependent on 14-3-3 eta function in neurodegeneration.