Activation of protein kinase C delta (PKC delta) has been linked to the neuroinflammation but the relationship with the various neurodegenerative diseases including the Alzheimer's disease (AD) was mostly elusive. In the AD brains, the special phospholipids, ethanolamine plasmalogens (Pis), were found to be reduced and our previous study showed that these lipids possess neuroprotective and anti-inflammatory functions. In the present study, we could find that these lipids can significantly attenuate the microglial expression of PKG delta in the neuroinflammation model and in the AD model mice brains. We also show an increase of PKC delta in the human postmortem AD brains. In addition, we also report that scallop derived Pls (sP1s) inhibited the p38MAPK and JNK protein expression which are involved in the expressional regulation of PKCS in the microglial cells. In addition, the lentiviral shRNA-mediated knockdown of PKCS attenuated the LPS-induced p65 (NF-kB) activation and inflammatory cytokine expression, suggesting that the PKCS can induce the inflammatory response which can be inhibited by the sPls. Taken together, our recent findings suggest that the sPls can attenuate the increased expression of PKCS associated with the neuro-inflammation in the murine brain. (C) 2018 Elsevier Inc. All rights reserved.