ABSTRACT
Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular homeostasis including neural transmission. Therefore, reductions of plasmalogens have been associated with neurodegenerative disorders, such as Alzheimer's disease (AD). To evaluate the potential protective effects of plasmalogens against the pathology of AD, protein expression levels of key factors in amyloid precursor protein (APP) metabolic processes were examined using human neuroblastoma SH-SY5Y cells. Here, phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) was shown to reduce protein expression levels of ß-site APP cleaving enzyme 1 (BACE1), clusterin, and Tau, factors involved in the amyloid ß-associated pathogenesis of AD. Thus, PC-PLS-18 may have preventive effects against AD by delaying the onset risk for a certain period.
Subject(s)
Alzheimer Disease , Neuroblastoma , Humans , Amyloid beta-Peptides/metabolism , Amyloid Precursor Protein Secretases/metabolism , Plasmalogens , Aspartic Acid Endopeptidases/metabolism , Oleic Acid , Phosphatidylcholines/pharmacology , Neuroblastoma/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolismABSTRACT
Plasmalogens are a group of glycerophospholipids containing a vinyl-ether bond at the sn-1 position in the glycerol backbone. Cellular membrane plasmalogens are considered to have important roles in homeostasis as endogenous antioxidants, differentiation, and intracellular signal transduction pathways including neural transmission. Therefore, reduced levels of plasmalogens have been suggested to be associated with neurodegenerative diseases such as Alzheimer's disease. Interestingly, although arachidonic acid is considered to be involved in learning and memory, it could be liberated and excessively activate neuronal activity to the excitotoxic levels seen in Alzheimer's disease patients. Here, we examined the protective effects of several kinds of plasmalogens against cellular toxicity caused by arachidonic acid in human neuroblastoma SH-SY5Y cells. As a result, only phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) showed protective effects against arachidonic acid-induced cytotoxicity based on the results of lactate dehydrogenase release and ATP depletion assays, as well as cellular morphological changes in SH-SY5Y cells. These results indicate that PC-PLS-18 protects against arachidonic acid-induced cytotoxicity, possibly via improving the stability of the cellular membrane in SH-SY5Y cells.
